Incretin dysfunction in type 2 diabetes: Clinical impact and future perspectives

Diabetes and Metabolism

Volumn 39, Issue 3, 2013, Pages 195-201

  Ahren B ^a  

^a LUND UNIVERSITY   (Sweden)

Author keywords

GIP; GLP 1; Incretin; Insulin; Type 2 diabetes

Indexed keywords

GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; INCRETIN; INSULIN;

BARIATRIC SURGERY; CELL FUNCTION; DIABETIC PATIENT; GLUCOSE BLOOD LEVEL; GLUCOSE INTOLERANCE; HEREDITY; HORMONE RESISTANCE; HUMAN; INSULIN LIKE ACTIVITY; INSULIN RELEASE; INSULIN RESPONSE; INTRAVENOUS GLUCOSE TOLERANCE TEST; MEAL; MOLECULAR MECHANICS; NON INSULIN DEPENDENT DIABETES MELLITUS; ORAL GLUCOSE TOLERANCE TEST; PANCREAS ISLET BETA CELL; REVIEW; STOMACH EMPTYING;

DIABETES MELLITUS, TYPE 2; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE 1; HUMANS; INCRETINS; INSULIN;

EID: 84878753499     PISSN: 12623636     EISSN: 18781780     Source Type: Journal    
DOI: 10.1016/j.diabet.2013.03.001     Document Type: Review

References (56)

1. LaBarre J. Sur les possibilités d'un traitement du diabète par l'incrétine. Bull Acad R Med Belg 1932, 12:620-634.
2. Heller H. Über das insulinotrope Hormon der Darmschleimhaut (Duodenin). Arch Exp Pharmakol 1935, 177:127-133.
3. Gutniak M., Ørskov C., Holst J., Ahrén B., Efendic S. Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus. N Engl J Med 1992, 326:1316-1322.
4. Ahrén B. GLP-1 for type 2 diabetes. Exp Cell Res 2011, 317:1239-1245.
5. McIntyre N., Holdsworth C.D., Turner D.S. New interpretation of oral glucose tolerance. Lancet 1964, 2:20-21.
6. Elrick H., Stimmler L., Hlad C.J.JJr, Arai Y. Plasma insulin responses to oral and intravenous glucose administration. J Clin Endocrinol Metab 1964, 24:2076-2082.
7. Nauck M.A., Homberger E., Siegel E.G., Allen R.C., Eaton R.P., Ebert R., et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 1986, 63:492-498.
8. Ahrén B., Winzell M.S., Pacini G. The augmenting effect on insulin secretion by oral versus intravenous glucose is exaggerated by high-fat diet in mice. J Endocrinol 2008, 197:181-187.
9. Bagger J.I., Knop F.K., Lund A., Vestergaard H., Holst J.J., Vilsbøll T. Impaired regulation of the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab 2011, 96:737-745.
10. Knop F.K., Vilsbøll T., Højberg P.V., Larsen S., Madsbad S., Vølund A., et al. Reduced incretin effect in type 2 diabetes. Cause or consequence of the diabetic state?. Diabetes 2007, 56:1951-1959.
11. Vardarli I., Nauck M.A., Köthe L.D., Deacon C.F., Holst J.J., Schweizer A., et al. Inhibition of DPP-4 with vildagliptin improved insulin secretion in response to oral as well as isoglycemic intravenous glucose without numerically changing the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab 2011, 96:945-954.
12. Ahrén B. The dynamic incretin adaptation and type 2 diabetes. J Clin Endocrinol Metab 2011, 96:620-622.
13. Nauck M.A., El-Ouaghlidi A., Gabrys B., Hucking K., Holst J.J., Deacon C.F., 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.
14. Muscelli E., Mari A., Natali A., Astiarraga B.D., Camastra S., Frascerra S., et al. Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance. Am J Physiol Endocrinol Metab 2006, 291:E1144-E1150.
15. Deacon C.F., Ahrén B. Physiology of incretins in health and disease. Rev Diabet Stud 2011, 8(3):293-306.
16. Lindgren O., Mari A., Deacon C.F., Carr R.D., Winzell M.S., Vikman J., et al. Differential islet and incretin hormone responses in morning versus afternoon after standardized meal in healthy men. J Clin Endocrinol Metab 2009, 94:2887-2892.
17. Ahren B., Carr R.D., Deacon C.F. Incretin hormone secretion over the day. Vitam Horm 2010, 84:203-220.
18. Holst J.J., Knop F.K., Vilsbøll T., Krarup T., Madsbad S. Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes. Diabetes Care 2011, 34(Suppl. 2):S251-S257.
19. Meier J.J., Nauck M.A. Is the diminished incretin effect in type 2 diabetes just an epi-phenomenon of impaired β-cell function. Diabetes 2010, 59:1117-1125.
20. Vilsbøll T., Krarup T., Deacon C.F., Madsbad S., Holst J.J. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 2001, 50:609-613.
21. Toft-Nielsen M.B., Damholt M.B., Madsbad S., Hilsted L.M., Hughes T.E., Michelsen B.K., 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.
22. Vollmer K., Holst J.J., Baller B., Ellrichmann M., Nauck M.A., Schmidt W.E., et al. Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 2008, 57:678-687.
23. Nauck M.A., Vardarli I., Deacon C.F., Holst J.J., Meier J.J. Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?. Diabetologia 2011, 54:10-18.
24. Carr R.D., Larsen M.O., Sörhede Winzell M., Jelic K., Lindgren O., Deacon C.F., et al. Incretin and islet hormonal responses to fat and protein ingestion in healthy men. Am J Physiol 2008, 295:E779-E784.
25. Carr R.D., Larsen M.O., Jelic K., Lindgren O., Vikman J., Holst J.J., et al. Secretion and dipeptidyl peptidase-4-mediated metabolism of incretin hormones after a mixed meal or glucose ingestion in obese compared to lean, non-diabetic, men. J Clin Endocrinol Metab 2010, 95:872-878.
26. Lindgren O., Carr R.D., Holst J.J., Deacon C.F., Ahrén B. Dissociated incretin hormone response to protein versus fat ingestion in obese subjects. Diabetes Obes Metab 2011, 13:863-865.
27. Ahlkvist L., Vikman J., Pacini G., Ahrén B. Synergism by individual macronutrients explains the marked early GLP-1 and islet hormone responses to mixed meal challenge in mice. Regul Pept 2012, 178:29-35.
28. Mussig K., Staiger H., Machicao F., Kirchhoff K., Guthoff M., Schäfer S.A., et al. Association of type 2 diabetes candidate polymorphisms in KCNQ1 with incretin and insulin secretion. Diabetes 2009, 58:1715-1720.
29. Rask E., Olsson T., Söderberg S., Johnson O., Seckl J., Holst J.J., et al. Impaired incretin responses after mixed meal is associated with insulin resistance in nondiabetic men. Diabetes Care 2001, 24:1640-1645.
30. Ahrén B., Larsson H., Holst J.J. Reduced gastric inhibitory polypeptide but normal glucagon-like peptide 1 response to oral glucose in postmenopausal women with impaired glucose tolerance. Eur J Endocrinol 1997, 137:127-131.
31. Rask E., Olsson T., Söderberg S., Holst J.J., Tura A., Pacini G., et al. Insulin secretion and incretin hormones after oral glucose in non-obese subjects with impaired glucose tolerance. Metabolism 2004, 53:624-631.
32. Miholic J., Orskov C., Holst J.J., Kotzerke J., Meyer H.J. Emptying of the gastric substitute, glucagon-like peptide-1 (GLP-1), and reactive hypoglycaemia after total gastrectomy. Dig Dis Sci 1991, 36:1361-1370.
33. Neff K.J., O'Shea D., le Roux C.W. Glucagon-like peptide-1 (GLP-1) dynamics following bariatric surgery: a signpost to a new frontier. Curr Diabet Rev 2013, 9:93-101.
34. Migoya E.M., Bergeron R., Miller J.L., Snyder R.N., Tanen M., Hiliard D., et al. Dipeptidyl peptidase-4 inhibition administered in combination with metformin result in an additive increase in the plasma concentrations of active GLP-1. Clin Pharmacol Ther 2010, 88:801-808.
35. Kappe C., Patrone C., Holst J.J., Zhang Q., Sjöholm Å. Metformin protects against lipoapoptosis and enhances GLP-1 secretion from GLP-1-producing cells. J Gastroenterol 2012, [in press]. 10.1007/s00535-012-0637-5.
36. Krarup T., Saurbrey N., Moody A.J., Kuhl C., Madsbad S. Effect of porcine gastric inhibitory polypeptide on β-cell function in type I and type II diabetes mellitus. Metabolism 1987, 36:677-682.
37. Nauck M.A., Heimesaat M.M., Orskov C., Holst J.J., Ebert R., Creutzfeldt W. Preserved incretin activity of glucagon-like peptide I [(7-36) amide] but not of synthetic human gastric inhibitory polypeptide in patients with type 2 diabetes mellitus. J Clin Invest 1993, 91:301-307.
38. Meier J.J., Nauck M.A., Siepmann N., Greulich M., Holst J.J., Deacon C.F., et al. Similar insulin secretory response to a gastric inhibitory polypeptide bolus injections at euglycaemia in first-degree relatives of patients with type 2 diabetes and control subjects. Metabolism 2003, 52:1579-1585.
39. Meier J.J., Gallwitz B., Askenas M., Vollmer K., Deacon C.F., Holst J.J., 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.
40. Knop F.K., Højberg Vilsbøll T.P.V., Larsen S., Madsbad S., Holst J.J. 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.
41. Hansen K.B., Vilsbøll T., Bagger J.I., Holst J.J., Knop F.K. Impaired incretin-induced amplification of insulin secretion after glucose homeostatic dysregulation in healthy subjects. J Clin Endocrinol Metab 2012, 97:13634-13670.
42. Højberg P.V., Vilsbøll T., Rabøl R., Knop F.K., Bache M., Krarup T., et al. Four weeks of near-normalisation 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.
43. Kjems L.L., Holst J.J., Vølund A., Madsbad S. 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.
44. Fritsche A., Stefan N., Hardt E., Häring H., Stumvoll M. Characterization of beta-cell dysfunction of impaired glucose tolerance: evidence for impairment of incretin-induced insulin secretion. Diabetologia 2000, 43:852-858.
45. Stumvoll M., Fritsche A., Häring H.U. Clinical characterization of insulin secretion as the basis for genetic analyses. Diabetes 2002, 51(Suppl. 1):S122-S129.
46. Simonsson E., Ahrén B. Potentiated beta-cell response to non-glucose stimuli in insulin-resistance C57BL/6J mice. Eur J Pharmacol 1998, 350:243-250.
47. Kang Z.F., Deng Y., Zhou Y., Fan R.R., Chan J.C.N., Laybutt D.R., et al. Pharmacological reduction of NEFA restores the efficacy of incretin-based therapies through GLP-1 receptor signaling in the beta cell in mouse models of diabetes. Diabetologia 2013, 56:423-433.
48. Mussig K., Staiger H., Machicao F., Häring H.U., Fritsche A. Genetic variants affecting incretin sensitivity and incretin secretion. Diabetologia 2010, 53:2289-2297.
49. Herzberg-Schäfer S., Heniu M., Stefan N., Häring H.U., Fritsche A. Impairment of GLP-1-induced insulin secretion: role of genetic background, insulin resistance and hyperglycaemia. Diabetes Obes Metab 2012, 14(Suppl. 3):85-90.
50. Simonis-Bik A.M., Eekhoff E.M., de Moor M.H., Kramer M.H., Boomsma D.I., Heine R.J., et al. Genetic influences on the insulin response of the beta cell to different secretagogues. Diabetologia 2009, 52:2570-2577.
51. Ahrén B. GLP-1 based therapy for type 2 diabetes: GLP-1 mimetics and DPP-IV inhibitors. Curr Diab Rep 2007, 7:340-347.
52. Ahrén B. Incretin therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors. Eur Diabetes Nursing 2013, 10:31-36.
53. Ahrén B. Type 2 diabetes, insulin secretion and β-cell mass. Curr Mol Med 2005, 5:275-286.
54. Unger R.H., Cherrington A.D. Glucagoncentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J Clin Invest 2012, 122:4-12.
55. UK Prospective Diabetes Study Group.UKPDS 16 Overview of 6 year's therapy of type II diabetes: a progressive disease. Diabetes 1995, 44:1249-1258.
56. Gallwitz B., Guzman J., Dotta F., Guerci B., Simo R., Basson B.R., et al. Exenatide twice daily versus glimepiride for prevention of glycaemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA): an open-label, randomized, controlled trial. Lancet 2012, 379:2270-2278.