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33644618433
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The biology of incretin hormones
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Drucker D: The biology of incretin hormones. Cell Metab 2006, 3:153-165.
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Cell Metab
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Drucker, D.1
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3
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0038310124
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Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells
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Anini Y, Brubaker PL: Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells. Endocrinology 2003, 144:3244-3250.
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(2003)
Endocrinology
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Anini, Y.1
Brubaker, P.L.2
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4
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48149095074
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Targeting GLP-1 release as a potential strategy for the therapy of type 2 diabetes
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This is a comprehensive review of GLP-1, its different physiologic effects, the mechanisms underlying GLP-1 secretion, and therapeutic implications in the treatment of type 2 diabetes
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Gribble FM: Targeting GLP-1 release as a potential strategy for the therapy of type 2 diabetes. Diabet Med 2008, 25:889-894. This is a comprehensive review of GLP-1, its different physiologic effects, the mechanisms underlying GLP-1 secretion, and therapeutic implications in the treatment of type 2 diabetes.
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Diabet Med
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Gribble, F.M.1
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5
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58149373780
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Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects
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This study compared the incretin response to oral glutamine in eight lean, eight obese nondiabetic, and eight obese subjects with type 2 diabetes or IGT. Glutamine was found to increase circulating GLP-1, GIP, and insulin concentrations in all three groups
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Greenfield JR, Farooqi IS, Keogh JM, et al.: Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. Am J Clin Nutr 2009, 89:105-113. This study compared the incretin response to oral glutamine in eight lean, eight obese nondiabetic, and eight obese subjects with type 2 diabetes or IGT. Glutamine was found to increase circulating GLP-1, GIP, and insulin concentrations in all three groups.
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(2009)
Am J Clin Nutr
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Greenfield, J.R.1
Farooqi, I.S.2
Keogh, J.M.3
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6
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9444244529
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Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes
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Nauck MA, Baller B, Meier JJ: Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes. Diabetes 2004, 53(Suppl 3):S190-S196.
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Diabetes
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Nauck, M.A.1
Baller, B.2
Meier, J.J.3
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7
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0000385121
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Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in humans
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Schirra J, Sturm K, Leicht P, et al.: Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in humans. J Clin Invest 1998, 101:1421-1430.
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Schirra, J.1
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8
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Endogenous glucagonlike peptide 1 controls endocrine pancreatic secretion and antropyloro- duodenal motility in humans
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Schirra J, Nicolaus M, Roggel R, et al.: Endogenous glucagonlike peptide 1 controls endocrine pancreatic secretion and antropyloro- duodenal motility in humans. Gut 2006, 55:243-251.
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Gut
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Schirra, J.1
Nicolaus, M.2
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9
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0038574573
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Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia
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Meier JJ, Gallwitz B, Siepmann N, et al.: Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia 2003, 46:798-801.
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Diabetologia
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Meier, J.J.1
Gallwitz, B.2
Siepmann, N.3
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10
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33847634679
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Suppression of glucagon secretion is lower after oral glucose administration than during intravenous glucose administration in human subjects
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This study looked at 16 firstdegree relatives of patients with type 2 diabetes and 10 controls during oral glucose tolerance test (OGTT) and IV glucose infusions. Glucagon levels were significantly suppressed in both experiments but the suppression was more pronounced during the IV glucose infusion. The differences between glucagon responses to oral and IV glucose correlated with GIP and GLP-1 levels. There were no differences in glucagon levels between the groups
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Meier JJ, Deacon CF, Schmidt WE, et al.: Suppression of glucagon secretion is lower after oral glucose administration than during intravenous glucose administration in human subjects. Diabetologia 2007, 50: 806-813. This study looked at 16 firstdegree relatives of patients with type 2 diabetes and 10 controls during oral glucose tolerance test (OGTT) and IV glucose infusions. Glucagon levels were significantly suppressed in both experiments but the suppression was more pronounced during the IV glucose infusion. The differences between glucagon responses to oral and IV glucose correlated with GIP and GLP-1 levels. There were no differences in glucagon levels between the groups.
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(2007)
Diabetologia
, vol.50
, pp. 806-813
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Meier, J.J.1
Deacon, C.F.2
Schmidt, W.E.3
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11
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75149127635
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Endogenous glucagon-like peptide-1 slows gastric emptying in healthy subjects, attenuating postprandial glycemia
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Ten healthy fasted subjects were randomized to receive a GLP-1 antagonist exendin(9-39) infusion or placebo. It was found that the GLP-1 antagonist accelerated gastric emptying and increased the glycemic response to a mashed potato meal, suggesting that GLP-1 plays a physiologic role to slow gastric emptying in health, which impacts on glucose absorption and postprandial glycemia
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Dean AM, Nguyen NQ, Stevens JE, et al.: Endogenous glucagon-like peptide-1 slows gastric emptying in healthy subjects, attenuating postprandial glycemia. J Clin Endocrinol Metab 2010, 95:215-221. Ten healthy fasted subjects were randomized to receive a GLP-1 antagonist exendin(9-39) infusion or placebo. It was found that the GLP-1 antagonist accelerated gastric emptying and increased the glycemic response to a mashed potato meal, suggesting that GLP-1 plays a physiologic role to slow gastric emptying in health, which impacts on glucose absorption and postprandial glycemia.
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(2010)
J Clin Endocrinol Metab
, vol.95
, pp. 215-221
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Dean, A.M.1
Nguyen, N.Q.2
Stevens, J.E.3
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12
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0029859220
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Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats
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Tang-Christensen M, Larsen PJ, Goke R, et al.: Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats. Am J Physiol 1996, 271(4 Pt 2): R848-R856.
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Tang-Christensen, M.1
Larsen, P.J.2
Goke, R.3
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13
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0033512486
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Glucagon-like peptide 1 and exendin-4 convert pancreatic AR42J cells into glucagon-and insulin-producing cells
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Zhou J, Wang X, Pineyro MA, Egan JM: Glucagon-like peptide 1 and exendin-4 convert pancreatic AR42J cells into glucagon-and insulin-producing cells. Diabetes 1999, 48: 2358-366.
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(1999)
Diabetes
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Zhou, J.1
Wang, X.2
Pineyro, M.A.3
Egan, J.M.4
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14
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0034522773
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Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, glucose-intolerant rats
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Perfetti R, Zhou J, Doyle ME, Egan JM: Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, glucose-intolerant rats. Endocrinology 2000, 141:4600-4605.
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Endocrinology
, vol.141
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Perfetti, R.1
Zhou, J.2
Doyle, M.E.3
Egan, J.M.4
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15
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Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic isletderived progenitor cells into insulin-producing cells
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Abraham EJ, Leech CA, Lin JC, et al.: Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic isletderived progenitor cells into insulin-producing cells. Endocrinology 2002, 143:3152-3161.
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Abraham, E.J.1
Leech, C.A.2
Lin, J.C.3
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16
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Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes
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Butler AE, Janson J, Bonner-Weir S, et al.: Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003, 52:102-110.
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Butler, A.E.1
Janson, J.2
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17
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0014951784
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Abnormal alpha-cell function in diabetes. Response to carbohydrate and protein ingestion
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Muller WA, Faloona GR, Aguilar-Parada E, Unger RH: Abnormal alpha-cell function in diabetes. Response to carbohydrate and protein ingestion. N Engl J Med 1970, 283:109-115.
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Muller, W.A.1
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Unger, R.H.4
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18
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0022617246
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Reduced incretin effect in type 2 (non-insulin-dependent) diabetes
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Nauck M, Stockmann F, Ebert R, Creutzfeldt W: Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 1986, 29:46-52.
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Diabetologia
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Nauck, M.1
Stockmann, F.2
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Creutzfeldt, W.4
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19
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5644221730
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Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral glucose in first-degree relatives of patients with type 2 diabetes
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Nauck MA, El-Ouaghlidi A, Gabrys B, et al.: Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral glucose in first-degree relatives of patients with type 2 diabetes. Regul Pept 2004, 122:209-217.
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Regul Pept
, vol.122
, pp. 209-217
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Nauck, M.A.1
El-Ouaghlidi, A.2
Gabrys, B.3
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20
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24944459820
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Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes
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Meier JJ, Gallwitz B, Askenas M, et al.: Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes. Diabetologia 2005, 48:1872-1881.
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Diabetologia
, vol.48
, pp. 1872-1881
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Meier, J.J.1
Gallwitz, B.2
Askenas, M.3
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21
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33847014543
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Normal secretion of the incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 during gestational diabetes mellitus
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Thirteen women with gestational diabetes and 13 controls were evaluated during an OGTT. No significant differences in GIP and GLP-1 responses were found between the two groups at any time of the study
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Cypryk K, Vilsboll T, Nadel I, et al.: Normal secretion of the incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 during gestational diabetes mellitus. Gynecol Endocrinol 2007, 23:58-62. Thirteen women with gestational diabetes and 13 controls were evaluated during an OGTT. No significant differences in GIP and GLP-1 responses were found between the two groups at any time of the study.
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Gynecol Endocrinol
, vol.23
, pp. 58-62
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Cypryk, K.1
Vilsboll, T.2
Nadel, I.3
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22
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48449093468
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Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients
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This study examined the incretin effect by performing oral and IV glucose tolerance tests in patients with normal glucose tolerance, IGT, and type 2 diabetes. It was found that glucose intolerance and obesity impair the incretin effect independently of one another and in an additive manner. Furthermore, glucagon suppression was found to be blunted in diabetic patients
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Muscelli E, Mari A, Casolaro A, et al.: Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients. Diabetes 2008, 57:1340-1348. This study examined the incretin effect by performing oral and IV glucose tolerance tests in patients with normal glucose tolerance, IGT, and type 2 diabetes. It was found that glucose intolerance and obesity impair the incretin effect independently of one another and in an additive manner. Furthermore, glucagon suppression was found to be blunted in diabetic patients.
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(2008)
Diabetes
, vol.57
, pp. 1340-1348
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Muscelli, E.1
Mari, A.2
Casolaro, A.3
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23
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33845383843
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Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance
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Muscelli E, Mari A, Natali A, et al.: Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance.AmJ Physiol EndocrinolMetab 2006, 291: E1144-E1150.
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(2006)
Am J Physiol EndocrinolMetab
, vol.291
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Muscelli, E.1
Mari, A.2
Natali, A.3
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24
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39049122631
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Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study
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This study assessed incretin levels in subjects with impaired fasting glucose as well as IGT. GLP-1 but not GIP levels were found to be reduced in individuals with abnormal glucose tolerance
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Laakso M, Zilinskaite J, Hansen T, et al.: Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study. Diabetologia 2008, 51:502-511. This study assessed incretin levels in subjects with impaired fasting glucose as well as IGT. GLP-1 but not GIP levels were found to be reduced in individuals with abnormal glucose tolerance.
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(2008)
Diabetologia
, vol.51
, pp. 502-511
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Laakso, M.1
Zilinskaite, J.2
Hansen, T.3
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25
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0034880655
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Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients
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Toft-Nielsen MB, Damholt MB, Madsbad S, et al.: Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001, 86:3717-3723.
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(2001)
J Clin Endocrinol Metab
, vol.86
, pp. 3717-3723
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Toft-Nielsen, M.B.1
Damholt, M.B.2
Madsbad, S.3
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26
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40949090627
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Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance
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Seventeen patients with mild type 2 diabetes, 17 with IGT, and 14 controls were assessed during an OGTT and mixed-meal challenge. GLP-1 levels were found to be the same in all three groups in both experiments. Also, GIP levels were similar after OGTT and there were no differences in integrated GIP levels after the meal
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Vollmer K, Holst JJ, Baller B, et al.: Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 2008, 57:678-687. Seventeen patients with mild type 2 diabetes, 17 with IGT, and 14 controls were assessed during an OGTT and mixed-meal challenge. GLP-1 levels were found to be the same in all three groups in both experiments. Also, GIP levels were similar after OGTT and there were no differences in integrated GIP levels after the meal.
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(2008)
Diabetes
, vol.57
, pp. 678-687
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Vollmer, K.1
Holst, J.J.2
Baller, B.3
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27
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0001095690
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Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients
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Vilsboll T, Krarup T, Deacon CF, et al.: Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 2001, 50:609-613.
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(2001)
Diabetes
, vol.50
, pp. 609-613
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Vilsboll, T.1
Krarup, T.2
Deacon, C.F.3
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28
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54549088705
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Is secretion of glucagon-like peptide-1 reduced in type 2 diabetes mellitus?
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This is a commentary summarizing the clinical data assessing GLP-1 secretion in type 2 diabetes and concluding that type 2 diabetes can develop without impairment in GLP-1 secretion, which appears to be a consequence rather than a cause of type 2 diabetes
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Meier JJ, Nauck MA: Is secretion of glucagon-like peptide-1 reduced in type 2 diabetes mellitus? Nat Clin Pract Endocrinol Metab 2008, 4:606-607. This is a commentary summarizing the clinical data assessing GLP-1 secretion in type 2 diabetes and concluding that type 2 diabetes can develop without impairment in GLP-1 secretion, which appears to be a consequence rather than a cause of type 2 diabetes.
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(2008)
Nat Clin Pract Endocrinol Metab
, vol.4
, pp. 606-607
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Meier, J.J.1
Nauck, M.A.2
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29
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0037241085
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Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects
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Vilsboll T, Agerso H, Krarup T, Holst JJ: Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab 2003, 88:220-224.
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(2003)
J Clin Endocrinol Metab
, vol.88
, pp. 220-224
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Vilsboll, T.1
Agerso, H.2
Krarup, T.3
Holst, J.J.4
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30
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33751506355
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The elimination rates of intact GIP as well as its primary metabolite, GIP 3-42, are similar in type 2 diabetic patients and healthy subjects
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Vilsboll T, Agerso H, Lauritsen T, et al.: The elimination rates of intact GIP as well as its primary metabolite, GIP 3-42, are similar in type 2 diabetic patients and healthy subjects. Regul Pept 2006, 137:168-172.
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(2006)
Regul Pept
, vol.137
, pp. 168-172
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Vilsboll, T.1
Agerso, H.2
Lauritsen, T.3
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31
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0036373430
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Defective amplification of the late phase insulin response to glucose by GIP in obese type II diabetic patients
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Vilsboll T, Krarup T, Madsbad S, Holst JJ: Defective amplification of the late phase insulin response to glucose by GIP in obese type II diabetic patients. Diabetologia 2002, 45:1111-1119.
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(2002)
Diabetologia
, vol.45
, pp. 1111-1119
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Vilsboll, T.1
Krarup, T.2
Madsbad, S.3
Holst, J.J.4
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32
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0037268159
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A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells
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Lynn FC, Thompson SA, Pospisilik JA, et al.: A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells. FASEB J 2003, 17:91-93.
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FASEB J
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Lynn, F.C.1
Thompson, S.A.2
Pospisilik, J.A.3
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33
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34249724553
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Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: Possible contribution to impaired incretin effects in diabetes
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Gene expression of incretin receptors was found to be significantly decreased in islets of pancreatectomized hyperglycemic rats, with recovery when glucose levels were normalized. This suggests that this is a likely mechanism contributing to the impaired incretin effects found in diabetes
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Xu G, Kaneto H, Laybutt DR, et al.: Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes. Diabetes 2007, 56:1551-1558. Gene expression of incretin receptors was found to be significantly decreased in islets of pancreatectomized hyperglycemic rats, with recovery when glucose levels were normalized. This suggests that this is a likely mechanism contributing to the impaired incretin effects found in diabetes.
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(2007)
Diabetes
, vol.56
, pp. 1551-1558
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Xu, G.1
Kaneto, H.2
Laybutt, D.R.3
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34
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0037312821
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The influence of GLP-1 on glucose-stimulated insulin secretion: Effects on beta-cell sensitivity in type 2 and nondiabetic subjects
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Kjems LL, Holst JJ, Volund A, Madsbad S: The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes 2003, 52:380-386.
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(2003)
Diabetes
, vol.52
, pp. 380-386
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Kjems, L.L.1
Holst, J.J.2
Volund, A.3
Madsbad, S.4
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35
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41149088656
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Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes
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This study investigated the effects of 4 weeks of near-normalization of blood glucose levels using insulin treatment in nine obese diabetic patients compared with nine controls. It was found that a supraphysiologic dose of GLP-1 enhances ß-cell responses to glucose in patients with type 2 diabetes, and near-normalization of blood glucose levels for 4 weeks further enhances ß-cell sensitivity and improves this effect
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Hojberg PV, Zander M, Vilsboll T, et al.: Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes. Diabetologia 2008, 51:632-640. This study investigated the effects of 4 weeks of near-normalization of blood glucose levels using insulin treatment in nine obese diabetic patients compared with nine controls. It was found that a supraphysiologic dose of GLP-1 enhances ß-cell responses to glucose in patients with type 2 diabetes, and near-normalization of blood glucose levels for 4 weeks further enhances ß-cell sensitivity and improves this effect.
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(2008)
Diabetologia
, vol.51
, pp. 632-640
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Hojberg, P.V.1
Zander, M.2
Vilsboll, T.3
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36
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73249122913
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Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus
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This study assessed the effect of GLP-1 infusions on glucagon secretion in 10 diabetic patients as well as healthy controls. There was a dose-dependent stepwise suppression of glucagon secretion in both patients and controls
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Hare KJ, Knop FK, Asmar M, et al.: Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus. J Clin Endocrinol Metab 2009, 94:4679-4687. This study assessed the effect of GLP-1 infusions on glucagon secretion in 10 diabetic patients as well as healthy controls. There was a dose-dependent stepwise suppression of glucagon secretion in both patients and controls.
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(2009)
J Clin Endocrinol Metab
, vol.94
, pp. 4679-4687
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Hare, K.J.1
Knop, F.K.2
Asmar, M.3
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37
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0029856880
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Gut incretin hormones in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM)-evidence for decreased glucagonlike peptide 1 secretion during oral glucose ingestion in NIDDM twins
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Vaag AA, Holst JJ, Volund A, Beck-Nielsen HB: Gut incretin hormones in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM)-evidence for decreased glucagonlike peptide 1 secretion during oral glucose ingestion in NIDDM twins. Eur J Endocrinol 1996, 135:425-432.
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Eur J Endocrinol
, vol.135
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Vaag, A.A.1
Holst, J.J.2
Volund, A.3
Beck-Nielsen, H.B.4
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38
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35648940236
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The insulinotropic effect of GIP is impaired in patients with chronic pancreatitis and secondary diabetes mellitus as compared to patients with chronic pancreatitis and normal glucose tolerance
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This study examined the effect of GIP in patients with diabetes secondary to chronic pancreatitis but not requiring insulin. Using hyperglycemic clamps and GIP infusions, it was found that there was a lack of GIP amplification of the late insulin response to IV glucose as glucose tolerance deteriorates in patients with chronic pancreatitis, suggesting that the same may be true for the loss of GIP effect in patients with type 2 diabetes
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Knop FK, Vilsboll T, Hojberg PV, et al.: The insulinotropic effect of GIP is impaired in patients with chronic pancreatitis and secondary diabetes mellitus as compared to patients with chronic pancreatitis and normal glucose tolerance. Regul Pept 2007, 144:123-130. This study examined the effect of GIP in patients with diabetes secondary to chronic pancreatitis but not requiring insulin. Using hyperglycemic clamps and GIP infusions, it was found that there was a lack of GIP amplification of the late insulin response to IV glucose as glucose tolerance deteriorates in patients with chronic pancreatitis, suggesting that the same may be true for the loss of GIP effect in patients with type 2 diabetes.
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(2007)
Regul Pept
, vol.144
, pp. 123-130
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Knop, F.K.1
Vilsboll, T.2
Hojberg, P.V.3
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39
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34547586659
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Reduced incretin effect in type 2 diabetes: Cause or consequence of the diabetic state?
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Knop FK, Vilsboll T, Hojberg PV, et al.: Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? Diabetes 2007, 56:1951-1959.
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(2007)
Diabetes
, vol.56
, pp. 1951-1959
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Knop, F.K.1
Vilsboll, T.2
Hojberg, P.V.3
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40
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65249174637
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Hyperglycemia acutely lowers the postprandial excursions of glucagon-like peptide-1 and gastric inhibitory polypeptide in humans
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Fifteen nondiabetic individuals participated in euglycemic and hyperglycemic clamps to assess the effects of acute hyperglycemia on the incretin response. It was found that the postprandial increases in GIP and GLP-1 following the administration of a mixed meal were about 50% lower during the experiments with hyperglycemia. Hyperglycemia also elicited a significant delay in gastric emptying
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Vollmer K, Gardiwal H, Menge BA, et al.: Hyperglycemia acutely lowers the postprandial excursions of glucagon-like peptide-1 and gastric inhibitory polypeptide in humans. J Clin Endocrinol Metab 2009, 94:1379-1385. Fifteen nondiabetic individuals participated in euglycemic and hyperglycemic clamps to assess the effects of acute hyperglycemia on the incretin response. It was found that the postprandial increases in GIP and GLP-1 following the administration of a mixed meal were about 50% lower during the experiments with hyperglycemia. Hyperglycemia also elicited a significant delay in gastric emptying.
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(2009)
J Clin Endocrinol Metab
, vol.94
, pp. 1379-1385
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Vollmer, K.1
Gardiwal, H.2
Menge, B.A.3
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41
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58149467276
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Four weeks of nearnormalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes
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This study evaluated the incretin effect in eight obese diabetic patients with poor glycemic control before and after 4 weeks of near-normalization of blood glucose levels using insulin treatment. After 4 weeks, it was found that ß-cell responsiveness to both GLP-1 and GIP improved by a factor of 3 to 4
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Hojberg PV, Vilsboll T, Rabol R, et al.: Four weeks of nearnormalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia 2009, 52:199-207. This study evaluated the incretin effect in eight obese diabetic patients with poor glycemic control before and after 4 weeks of near-normalization of blood glucose levels using insulin treatment. After 4 weeks, it was found that ß-cell responsiveness to both GLP-1 and GIP improved by a factor of 3 to 4.
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(2009)
Diabetologia
, vol.52
, pp. 199-207
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Hojberg, P.V.1
Vilsboll, T.2
Rabol, R.3
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42
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33847682160
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Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus
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Glucagon suppression responses were studied during OGTT and IV glucose infusion in 10 diabetic patients and 10 controls; these were found to be significantly attenuated and delayed only in the diabetic patients after oral ingestion of glucose, suggesting that this phenomenon contributes to both the glucose intolerance and reduced incretin effect observed in patients with type 2 diabetes
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Knop FK, Vilsboll T, Madsbad S, et al.: Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus. Diabetologia 2007, 50:797-805. Glucagon suppression responses were studied during OGTT and IV glucose infusion in 10 diabetic patients and 10 controls; these were found to be significantly attenuated and delayed only in the diabetic patients after oral ingestion of glucose, suggesting that this phenomenon contributes to both the glucose intolerance and reduced incretin effect observed in patients with type 2 diabetes.
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(2007)
Diabetologia
, vol.50
, pp. 797-805
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Knop, F.K.1
Vilsboll, T.2
Madsbad, S.3
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43
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33746075560
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TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program
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Florez JC, Jablonski KA, Bayley N, et al.: TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med 2006, 355:241-250.
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(2006)
N Engl J Med
, vol.355
, pp. 241-250
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Florez, J.C.1
Jablonski, K.A.2
Bayley, N.3
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44
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33750892139
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Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals
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Saxena R, Gianniny L, Burtt NP, et al.: Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals. Diabetes 2006, 55:2890-2895.
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(2006)
Diabetes
, vol.55
, pp. 2890-2895
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Saxena, R.1
Gianniny, L.2
Burtt, N.P.3
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45
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35748976848
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Genome-wide association with diabetes-related traits in the framingham heart study
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Meigs JB, Manning AK, Fox CS, et al.: Genome-wide association with diabetes-related traits in the Framingham Heart Study. BMC Med Genet 2007, 8(Suppl 1):S16.
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(2007)
BMC Med Genet
, vol.8
, Issue.SUPPL. 1
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Meigs, J.B.1
Manning, A.K.2
Fox, C.S.3
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46
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66549087600
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Genetic architecture of type 2 diabetes: Recent progress and clinical implications
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This review article focuses on the recent genetic discoveries pertaining to polygenic type 2 diabetes
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Grant RW, Moore AF, Florez JC: Genetic architecture of type 2 diabetes: recent progress and clinical implications. Diabetes Care 2009, 32:1107-1114. This review article focuses on the recent genetic discoveries pertaining to polygenic type 2 diabetes.
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(2009)
Diabetes Care
, vol.32
, pp. 1107-1114
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Grant, R.W.1
Moore, A.F.2
Florez, J.C.3
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47
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35848942800
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Impaired glucagonlike peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms
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A total of 1110 nondiabetic German participants were genotyped for polymorphisms in TCF7L2 and underwent an OGTT to assess the incretin response. Two hundred and ten participants also underwent an IV glucose tolerance test. It was found that variants of TCF7L2 specifically impair GLP-1- induced insulin secretion, and this was likely due to a defect in GLP-1 signaling as opposed to a reduction in GLP-1 secretion
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Schafer SA, Tschritter O, Machicao F, et al.: Impaired glucagonlike peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Diabetologia 2007, 50:2443-2450. A total of 1110 nondiabetic German participants were genotyped for polymorphisms in TCF7L2 and underwent an OGTT to assess the incretin response. Two hundred and ten participants also underwent an IV glucose tolerance test. It was found that variants of TCF7L2 specifically impair GLP-1- induced insulin secretion, and this was likely due to a defect in GLP-1 signaling as opposed to a reduction in GLP-1 secretion.
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(2007)
Diabetologia
, vol.50
, pp. 2443-2450
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Schafer, S.A.1
Tschritter, O.2
Machicao, F.3
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48
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35848935206
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The enteroinsular axis may mediate the diabetogenic effects of TCF7L2 polymorphisms
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Nauck MA, Meier JJ: The enteroinsular axis may mediate the diabetogenic effects of TCF7L2 polymorphisms. Diabetologia 2007, 50:2413-2416.
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(2007)
Diabetologia
, vol.50
, pp. 2413-2416
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Nauck, M.A.1
Meier, J.J.2
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49
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67349102328
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The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men
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In this study, 81 healthy young Danish men underwent genotyping for the T allele of rs7903146 TCF7L2 along with various ß-cell tests. It was found that subjects with this genotype had reduced 24-hour insulin and glucagon concentrations, along with reduced insulin secretion during mixed meal testing and elevated hepatic glucose production
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Pilgaard K, Jensen CB, Schou JH, et al.: The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. Diabetologia 2009, 52:1298-1307. In this study, 81 healthy young Danish men underwent genotyping for the T allele of rs7903146 TCF7L2 along with various ß-cell tests. It was found that subjects with this genotype had reduced 24-hour insulin and glucagon concentrations, along with reduced insulin secretion during mixed meal testing and elevated hepatic glucose production.
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(2009)
Diabetologia
, vol.52
, pp. 1298-1307
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Pilgaard, K.1
Jensen, C.B.2
Schou, J.H.3
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50
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77449099615
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TCF7L2 variant rs7903146 affects the risk of type 2 diabetes by modulating incretin action
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This study evaluated eight subjects with risk-conferring TCF7L2 genotypes (TT or TC at rs7903146) and 10 matched subjects with wild-type genotype (CC). The incretin effect was assessed from ratios of the insulin secretory rates during oral and isoglycemic glucose infusions. ß- Cell responsivity to oral glucose was 50% lower in the group of subjects with risk-conferring TCF7L2 genotypes compared with control subjects. The incretin effect was also reduced by 30% in the at-risk group, suggesting that this genotypic variant affects the risk of type 2 diabetes, at least in part, by modifying the effect of incretins on insulin secretion
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Villereal DT, Robertson H, Bell GI, et al.: TCF7L2 variant rs7903146 affects the risk of type 2 diabetes by modulating incretin action. Diabetes 2010, 59:479-485. This study evaluated eight subjects with risk-conferring TCF7L2 genotypes (TT or TC at rs7903146) and 10 matched subjects with wild-type genotype (CC). The incretin effect was assessed from ratios of the insulin secretory rates during oral and isoglycemic glucose infusions. ß- Cell responsivity to oral glucose was 50% lower in the group of subjects with risk-conferring TCF7L2 genotypes compared with control subjects. The incretin effect was also reduced by 30% in the at-risk group, suggesting that this genotypic variant affects the risk of type 2 diabetes, at least in part, by modifying the effect of incretins on insulin secretion.
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(2010)
Diabetes
, vol.59
, pp. 479-485
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Villereal, D.T.1
Robertson, H.2
Bell, G.I.3
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51
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15444367142
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Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus
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Kolterman OG, Kim DD, Shen L, et al.: Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Syst Pharm 2005, 62:173-181.
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(2005)
Am J Health Syst Pharm
, vol.62
, pp. 173-181
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Kolterman, O.G.1
Kim, D.D.2
Shen, L.3
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52
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67649666737
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Liraglutide once a day versus exenatide twice a day for type 2 diabetes: A 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6)
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This is a 26-week trial comparing once-daily liraglutide with twice-daily exenatide in 233 diabetic patients who were uncontrolled on maximally tolerated doses of metformin, sulfonylurea, or both. This study revealed that liraglutide once a day provided significantly greater improvements in glycemic control than did exenatide twice a day and was generally better tolerated
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Buse JB, Rosenstock J, Sesti G, et al.: Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009, 374:39-47. This is a 26-week trial comparing once-daily liraglutide with twice-daily exenatide in 233 diabetic patients who were uncontrolled on maximally tolerated doses of metformin, sulfonylurea, or both. This study revealed that liraglutide once a day provided significantly greater improvements in glycemic control than did exenatide twice a day and was generally better tolerated.
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(2009)
Lancet
, vol.374
, pp. 39-47
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Buse, J.B.1
Rosenstock, J.2
Sesti, G.3
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53
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66249143015
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Liraglutide: A new treatment for type 2 diabetes
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Vilsboll T: Liraglutide: a new treatment for type 2 diabetes. Drugs Today (Barc) 2009, 45:101-113.
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(2009)
Drugs Today (Barc)
, vol.45
, pp. 101-113
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Vilsboll, T.1
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54
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39749143348
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Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and argininestimulated insulin secretion during hyperglycaemia in patients with type 2 diabetes mellitus
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Vilsboll T, Brock B, Perrild H, et al.: Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and argininestimulated insulin secretion during hyperglycaemia in patients with type 2 diabetes mellitus. Diabet Med 2008, 25:152-156.
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(2008)
Diabet Med
, vol.25
, pp. 152-156
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Vilsboll, T.1
Brock, B.2
Perrild, H.3
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55
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34249869806
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Liraglutide, a longacting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes
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Vilsboll T, Zdravkovic M, Le-Thi T, et al.: Liraglutide, a longacting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care 2007, 30:1608-1610.
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(2007)
Diabetes Care
, vol.30
, pp. 1608-1610
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Vilsboll, T.1
Zdravkovic, M.2
Le-Thi, T.3
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56
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38549162147
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Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years
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This randomized openlabel trial showed that adjunctive exenatide treatment for at least 3 years in patients with type 2 diabetes resulted in sustained improvements in glycemic control, cardiovascular risk factors, and hepatic biomarkers, coupled with progressive weight reduction
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Klonoff DC, Buse JB, Nielsen LL, et al.: Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008, 24:275-286. This randomized openlabel trial showed that adjunctive exenatide treatment for at least 3 years in patients with type 2 diabetes resulted in sustained improvements in glycemic control, cardiovascular risk factors, and hepatic biomarkers, coupled with progressive weight reduction.
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(2008)
Curr Med Res Opin
, vol.24
, pp. 275-286
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Klonoff, D.C.1
Buse, J.B.2
Nielsen, L.L.3
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57
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34249891874
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Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes
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This is a 15-week randomized clinical trial that evaluated the effect of lower and higherdose exenatide LAR administered to 45 diabetic subjects with suboptimal glycemic control on metformin and/or diet and exercise. It was found that subjects receiving exenatide LAR had significant reductions in mean HbA1c compared with placebo, and subjects receiving the higher dose of exenatide LAR also had significant reductions in mean weight compared with the other two groups
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Kim D, MacConell L, Zhuang D, et al.: Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care 2007, 30:1487-1493. This is a 15-week randomized clinical trial that evaluated the effect of lower and higherdose exenatide LAR administered to 45 diabetic subjects with suboptimal glycemic control on metformin and/or diet and exercise. It was found that subjects receiving exenatide LAR had significant reductions in mean HbA1c compared with placebo, and subjects receiving the higher dose of exenatide LAR also had significant reductions in mean weight compared with the other two groups.
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(2007)
Diabetes Care
, vol.30
, pp. 1487-1493
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Kim, D.1
MacConell, L.2
Zhuang, D.3
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58
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69949102359
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Clinical results of treating type 2 diabetic patients with sitagliptin, vildagliptin or saxagliptin-diabetes control and potential adverse events
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This is an excellent current review of the three available DPP-4 inhibitors that summarizes the results of the clinical studies demonstrating the efficacy and safety data for these agents
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Ahren B: Clinical results of treating type 2 diabetic patients with sitagliptin, vildagliptin or saxagliptin-diabetes control and potential adverse events. Best Pract Res Clin Endocrinol Metab 2009, 23:487-498. This is an excellent current review of the three available DPP-4 inhibitors that summarizes the results of the clinical studies demonstrating the efficacy and safety data for these agents.
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(2009)
Best Pract Res Clin Endocrinol Metab
, vol.23
, pp. 487-498
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Ahren, B.1
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