Emerging cardiovascular actions of the incretin hormone glucagon-like peptide-1: Potential therapeutic benefits beyond glycaemic control?

British Journal of Pharmacology

Volumn 157, Issue 8, 2009, Pages 1340-1351

  Grieve, David J ^a   Cassidy, Roslyn S ^a   Green, Brian D ^b  

^a QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

^b QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

Author keywords

Cardiac ischaemia; Diabetes; Glucagon like peptide 1; Glucagon like peptide 1 receptor; Heart failure; Incretin; Sympathetic activation; Vasodilatation

Indexed keywords

ALBIGLUTIDE; ANTIDIABETIC AGENT; BIM 51077; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN (9-39); EXENDIN 4; GLUCAGON LIKE PEPTIDE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 DERIVATIVE; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; LIRAGLUTIDE; MKC 253; SITAGLIPTIN; TASPOGLUTIDE; UNCLASSIFIED DRUG; VICTOZA;

ALZHEIMER DISEASE; ANGIOPLASTY; BINDING AFFINITY; BLOOD PRESSURE; CARDIOMYOPATHY; CARDIOVASCULAR FUNCTION; CLINICAL TRIAL; DRUG BINDING; DRUG CLEARANCE; DRUG FORMULATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; ENDOTHELIAL DYSFUNCTION; GLUCOSE TRANSPORT; GLYCEMIC CONTROL; HEART FAILURE; HEART INFARCTION; HEART MUSCLE CONTRACTILITY; HEART MUSCLE ISCHEMIA; HEART PROTECTION; HEART RATE; HUMAN; HUNTINGTON CHOREA; HYPERGLYCEMIA; INSULIN LIKE ACTIVITY; INSULIN SENSITIVITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PEPTIDE SYNTHESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN SECRETION; REVIEW; SEQUENCE HOMOLOGY; VASCULARIZATION;

ANIMALS; BLOOD GLUCOSE; CARDIOVASCULAR AGENTS; CARDIOVASCULAR DISEASES; CARDIOVASCULAR SYSTEM; DIABETES MELLITUS, TYPE 2; GLUCAGON-LIKE PEPTIDE 1; HUMANS; HYPOGLYCEMIC AGENTS; INCRETINS; INSULIN; RECEPTORS, GLUCAGON;

EID: 70350341465     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2009.00376.x     Document Type: Review

References (134)

1. Arnette D, Gibson TB, Lawrence MC, January B, Khoo S, McGlynn K et al. (2003). Regulation of ERK1 and ERK2 by glucose and peptide hormones in pancreatic b cells. J Biol Chem 278: 32517-32525. (Pubitemid 37055689)
2. Asbun J, Villarreal FJ (2006). The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy. J Am Coll Cardiol 47: 693-700.
3. Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M (2008). Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and-independent pathways. Circulation 117: 2340-2350.
4. Barragan JM, Rodriguez RE, Blazquez E (1994). Changes in arterial blood pressure and heart rate induced by glucagon-like peptide-1-(7-36) amide in rats. Am J Physiol Endocrinol Metab 266: E459-E466.
5. Barragan JM, Rodriguez RE, Eng J, Blazquez E (1996). Interactions of exendin-(9-39) with the effects of glucagon-like peptide-1-(7-36) amide and of exendin-4 on arterial blood pressure and heart rate in rats. Regul Pept 67: 63-68.
6. Barragan JM, Eng J, Rodriguez R, Blazquez E (1999). Neural contribution to the effect of glucagon-like peptide-1-(7-36) amide on arterial blood pressure in rats. Am J Physiol Endocrinol Metab 277: E784-E791.
7. Basu A, Charkoudian N, Schrage W, Rizza RA, Basu R, Joyner MJ (2007). Beneficial effects of GLP-1 on endothelial function in humans: dampening by glyburide but not by glimepiride. Am J Physiol Endocrinol Metab 293: E1289-E1295.
8. Bell DSH (2003). Heart failure: the frequent, forgotten, and often fatal complication of diabetes. Diabetes Care 26: 2433-2441.
9. Bell GI, Sanchez-Pescador R, Laybourn PJ, Najarian RC (1983). Exon duplication and divergence in the human preproglucagon gene. Nature 304: 368-371.
10. Bojanowska E, Stempniak B (2000). Effects of centrally or systemically injected glucagon-like peptide-1(7-36) amide on release of neuro-hypophysial hormones and blood pressure in the rat. Regul Pept 91: 75-81.
11. Bojanowska E, Stempniak B (2002). Effects of glucagon-like peptide-1(7-36) amide on neurohypophysial and cardiovascular functions under hypo-or normotensive hypovolaemia in the rat. J Endocrinol 172: 303-310.
12. Bose AK, Mocanu MM, Carr RD, Brand CL, Yellon DM (2005a). Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes 54: 146-151.
13. Bose AK, Mocanu MM, Carr RD, Yellon DM (2005b). Glucagon like peptide-1 is protective against myocardial ischemia/reperfusion injury when given either as a preconditioning mimetic or at reper-fusion in an isolated rat heart model. Cardiovasc Drugs Ther 19: 9-11.
14. Bose A, Mocanu M, Carr R, Yellon D (2007). Myocardial ischaemia-reperfusion injury is attenuated by intact glucagon like peptide-1 (GLP-1) in the in vitro rat heart and may involve the p70s6K pathway. Cardiovasc Drugs Ther 21: 253-256.
15. Bullock BP, Heller RS, Habener JF (1996). Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. Endocrinology 137: 2968-2978.
16. Burcelin R, Da Costa A, Drucker D, Thorens B (2001). Glucose competence of the hepatoportal vein sensor requires the presence of an activated glucagon-like peptide-1 receptor. Diabetes 50: 1720-1728.
17. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD (2004). Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 27: 2628-2635.
18. Buteau J, Foisy S, Rhodes CJ, Carpenter L, Biden TJ, Prentki M (2001). Protein kinase Cz activation mediates glucagon-like peptide-1-induced pancreatic b-cell proliferation. Diabetes 50: 2237-2243.
19. Buteau J, Foisy S, Joly E, Prentki M (2003). Glucagon-like peptide 1 induces pancreatic b-cell proliferation via transactivation of the epidermal growth factor receptor. Diabetes 52: 124-132.
20. Chen D, Liao J, Li N, Zhou C, Liu Q, Wang G et al. (2007). A nonpep-tidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db/db mice. Proc Natl Acad Sci USA 104: 943-948.
21. Clements RS Jr, Bell DS (1985). Complications of diabetes. Prevalence, detection, current treatment, and prognosis. Am J Med 79: 2-7.
22. Colucci WS, Kolias TJ, Adams KF, Armstrong WF, Ghali JK, Gottlieb SS et al. (2007). Metoprolol reverses left ventricular remodeling in patients with asymptomatic systolic dysfunction: the reversal of ventricular remodeling with toprol-XL (REVERT) trial. Circulation 116: 49-56.
23. Creutzfeldt W (1979). The incretin concept today. Diabetologia 16: 75-85.
24. Creutzfeldt WO, Kleine N, Willms B, Orskov C, Holst JJ, Nauck MA (1996). Glucagonostatic actions and reduction of fasting hypergly-cemia by exogenous glucagon-like peptide I(7-36) amide in type I diabetic patients. Diabetes Care 19: 580-586.
25. Deacon CF (2004). Circulation and degradation of GIP and GLP-1. Horm Metab Res 36: 761-765.
26. Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ (1995). Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes 44: 1126-1131.
27. Deacon CF, Pridal L, Klarskov L, Olesen M, Holst JJ (1996). Glucagon-like peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig. Am J Physiol Endocrinol Metab 271: E458-E464.
28. Deacon CF, Plamboeck A, Moller S, Holst JJ (2002). GLP-1-(9-36) amide reduces blood glucose in anesthetized pigs by a mechanism that does not involve insulin secretion. Am J Physiol Endocrinol Metab 282: E873-E879.
29. Defronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD (2005). Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 28: 1092-1100.
30. Dhanvantari S, Seidah NG, Brubaker PL (1996). Role of prohormone convertases in the tissue-specific processing of proglucagon. Mol Endocrinol 10: 342-355.
31. Doyle ME, Greig NH, Holloway HW, Betkey JA, Bernier M, Egan JM (2001). Insertion of an N-terminal 6-aminohexanoic acid after the 7 amino acid position of glucagon-like peptide-1 produces a long-acting hypoglycemic agent. Endocrinology 142: 4462-4468.
32. Drucker DJ (2003). Glucagon-like peptide-1 and the islet b-cell: augmentation of cell proliferation and inhibition of apoptosis. Endocrinology 144: 5145-5148.
33. Drucker DJ (2006). The biology of incretin hormones. Cell Metab 3: 153-165.
34. Dubé PE, Brubaker PL (2004). Nutrient, neural and endocrine control of glucagon-like peptide secretion. Horm Metab Res 36: 755-760.
35. Edwards CM, Edwards AV, Bloom SR (1997). Cardiovascular and pancreatic endocrine responses to glucagon-like peptide-1(7-36) amide in the conscious calf. Exp Physiol 82: 709-716.
36. Eissele R, Göke R, Willemer S, Harthus HP, Vermeer H, Arnold R et al. (1992). Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 22: 283-291.
37. Elliott RM, Morgan LM, Tredger JA, Deacon S, Wright J, Marks V (1993). Glucagon-like peptide-1(7-36) amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. J Endocrinol 138: 159-166.
38. Fang ZY, Prins JB, Marwick TH (2004). Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocr Rev 25: 543-567.
39. Fehse F, Trautmann M, Holst JJ, Halseth AE, Nanayakkara N, Nielsen LL et al. (2005). Exenatide augments first-and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 90: 5991-5997.
40. Flatt PR, Bailey CJ, Green BD (2009). Recent advances in antidiabetic drug therapies targeting the enteroinsular axis. Curr Drug Metab 10: 125-137.
41. Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I et al. (2009). Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 373: 473-481.
42. Garcia MJ, Mcnamara PM, Gordon T, Kannel WB (1974). Morbidity and mortality in diabetics in the Framingham population. Sixteen year follow-up study. Diabetes 23: 105-111.
43. Gardiner SM, March JE, Kemp PA, Bennett T (2006). Mesenteric vaso-constriction and hindquarters vasodilatation accompany the pressor actions of exendin-4 in conscious rats. J Pharmacol Exp Ther 316: 852-859.
44. Gardiner SM, March JE, Kemp PA, Bennett T (2008). Autonomic nervous system-dependent and-independent cardiovascular effects of exendin-4 infusion in conscious rats. Br J Pharmacol 154: 60-71.
45. Gedulin BR, Nikoulina SE, Smith PA, Gedulin G, Nielsen LL, Baron AD et al. (2005). Exenatide (exendin-4) improves insulin sensitivity and b-cell mass in insulin-resistant obese fa/fa Zucker rats independent of glycemia and body weight. Endocrinology 146: 2069-2076.
46. Goke R, Fehmann HC, Linn T, Schmidt H, Krause M, Eng J et al. (1993). Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting b-cells. J Biol Chem 268: 19650-19655.
47. Golpon HA, Puechner A, Welte T, Wichert PV, Feddersen CO (2001). Vasorelaxant effect of glucagon-like peptide-(7-36) amide and amylin on the pulmonary circulation of the rat. Regul Pept 102: 81-86.
48. Green BD, Flatt PR (2007). Incretin hormone mimetics and analogues in diabetes therapeutics. Best Pract Res Clin Endocrinol Metab 21: 497-516.
49. Green BD, Gault VA, Irwin N, Mooney MH, Bailey CJ, Harriott P et al. (2003). Metabolic stability, receptor binding, cAMP generation, insulin secretion and antihyperglycaemic activity of novel N-terminal Glu9-substituted analogues of glucagon-like peptide-1. Biol Chem 384: 1543-1551.
50. Green BD, Gault VA, Flatt PR, Harriott P, Greer B, O'Harte FPM (2004a). Comparative effects of GLP-1 and GIP on cAMP production, insulin secretion, and in vivo antidiabetic actions following substitution of Ala8/Ala2 with 2-aminobutyric acid. Arch Biochem Biophys 428: 136-143.
51. Green BD, Gault VA, O'Harte FP, Flatt PR (2004b). Structurally modified analogues of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) as future antidiabetic agents. Curr Pharm Des 10: 3651-3662.
52. Green BD, Mooney MH, Gault VA, Irwin N, Bailey CJ, Harriott P et al. (2004c). Lys9 for Glu9 substitution in glucagon-like peptide-1(7-36) amide confers dipeptidylpeptidase IV resistance with cellular and metabolic actions similar to those of established antagonists glucagon-like peptide-1(9-36) amide and exendin(9-39). Metabolism 53: 252-259.
53. Green BD, Lavery KS, Irwin N, O'Harte FP, Harriott P, Greer B et al. (2006). Novel GLP-1 analogue (Val8) GLP-1 results in significant improvements of glucose tolerance and pancreatic b cell function after 3 weeks daily administration in obese diabetic (ob/ob) mice. J Pharmacol Exp Ther 318: 914-921.
54. Green BD, Flatt PR, Bailey CJ (2007). Dipeptidyl peptidase IV (DPP IV) inhibitors: a newly emerging drug class for the treatment of type 2 diabetes. Diab Vasc Dis Res 3: 159-165.
55. Green BD, Hand KV, Dougan JE, McDonnell BM, Cassidy RS, Grieve DJ (2008). GLP-1 and related peptides cause concentration-dependent relaxation of rat aorta through a pathway involving KATP and cAMP. Arch Biochem Biophys 478: 136-142.
56. Gribble F (2008). RD Lawrence lecture 2008: targeting GLP-1 release as a potential strategy for the therapy of type 2 diabetes. Diabet Med 25: 889-894.
57. Gros R, You X, Baggio LL, Kabir MG, Sadi AM, Mungrue IN et al. (2003). Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology 144: 2242-2252.
58. Gutniak MK, Linde B, Holst JJ, Efendic S (1994). Subcutaneous injection of the incretin hormone glucagon-like peptide 1 abolishes postprandial glycemia in NIDDM. Diabetes Care 17: 1039-1044.
59. Hargrove DM, Nardone NA, Persson LM, Parker JC, Stevenson RW (1995). Glucose-dependent action of glucagon-like peptide-1(7-37) in vivo during short-or long-term administration. Metabolism 44: 1231-1237.
60. Heinrich G, Gros P, Lund PK, Bentley RC, Habener JF (1984). Pre-proglucagon messenger ribonucleic acid: nucleotide and encoded amino acid sequences of the rat pancreatic complementary deox-yribonucleic acid. Endocrinology 115: 2176-2181.
61. Holscher C, Li L (2008). New roles for insulin-like hormones in neu-ronal signalling and protection: new hopes for novel treatments of Alzheimer's disease? Neurobiol Aging DOI: 10.1016/ j.neurobiolaging.2008.08.023 [Epub ahead of print].
62. Holz GG (2004). Epac: a new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic b-cell. Diabetes 53: 5-13.
63. Hupe-Sodmann K, McGregor GP, Bridenbaugh R, Goke R, Goke B, Thole H et al. (1995). Characterisation of the processing by human neutral endopeptidase 24.11 of GLP-1(7-36) amide and comparison of the substrate specificity of the enzyme for other glucagon-like peptides. Regul Pept 58: 149-156.
64. Hupe-Sodmann K, Goke R, Goke B, Thole HH, Zimmermann B, Voigt K et al. (1997). Endoproteolysis of glucagon-like peptide (GLP)-1(7-36) amide by ectopeptidases in RINm5F cells. Peptides 18: 625-632.
65. Hwa JJ, Ghibaudi L, Williams P, Witten MB, Tedesco R, Strader CD (1998). Differential effects of intracerebroventricular glucagon-like peptide-1 on feeding and energy expenditure regulation. Peptides 19: 869-875.
66. Idris I, Patiag D, Gray S, Donnelly R (2002). Exendin-4 increases insulin sensitivity via a PI-3-kinase-dependent mechanism: contrasting effects of GLP-1. Biochem Pharmacol 63: 993-996.
67. Isbil-Buyukcoskun N, Gulec G (2004). Effects of intracerebroventricu- larly injected glucagon-like peptide-1 on cardiovascular parameters; role of central cholinergic system and vasopressin. Regul Pept 118: 33-38.
68. Juntti-Berggren L, Pigon J, Karpe F, Hamsten A, Gutniak M, Vignati L et al. (1996). The antidiabetogenic effect of GLP-1 is maintained during a 7-day treatment period and improves diabetic dyslipopro-teinemia in NIDDM patients. Diabetes Care 19: 1200-1206.
69. Kang JH, Kim MJ, Jang HI, Koh KH, Yum KS, Rhie DJ et al. (2007). Proximal cyclic AMP response element is essential for exendin-4 induction of rat EGR-1 gene. Am J Physiol Endocrinol Metab 292: E215-E222.
70. Kannel WB, McGee DL (1979). Diabetes and cardiovascular disease. The Framingham study. JAMA 241: 2035-2038.
71. Kanse SM, Kreymann B, Ghatei MA, Bloom SR (1988). Identification and characterization of glucagon-like peptide-1 7-36 amide-binding sites in the rat brain and lung. FEBS Lett 241: 209-212.
72. Kavianipour M, Ehlers MR, Malmberg K, Ronquist G, Ryden L, Wik-strom G et al. (2003). Glucagon-like peptide-1(7-36) amide prevents the accumulation of pyruvate and lactate in the ischemic and non-ischemic porcine myocardium. Peptides 24: 569-578.
73. Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS et al. (2005). Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 28: 1083-1091.
74. Kervran A, Blache P, Bataille D (1987). Distribution of oxyntomodulin and glucagon in the gastrointestinal tract and the plasma of the rat. Endocrinology 121: 704-713.
75. Kieffer TJ, Habener JF (1999). The glucagon-like peptides. Endocr Rev 20: 876-913.
76. King H, Aubert RE, Herman WH (1998). Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 21: 1414-1431.
77. Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH et al. (2008). 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 24: 275-286.
78. Knudsen LB, Pridal L (1996). Glucagon-like peptide-1-(9-36) amide is a major metabolite of glucagon-like peptide-1-(7-36) amide after in vivo administration to dogs, and it acts as an antagonist on the pancreatic receptor. Eur J Pharmacol 318: 429-435.
79. Knudsen LB, Kiel D, Teng M, Behrens C, Bhumralkar D, Kodra JT et al. (2007). Small-molecule agonists for the glucagon-like peptide 1 receptor. Proc Natl Acad Sci USA 104: 937-942.
80. Kolterman OG, Buse JB, Fineman MS, Gaines E, Heintz S, Bicsak TA et al. (2003). Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 88: 3082-3089.
81. Larsson H, Holst JJ, Ahrén B (1997). Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans. Acta Physiol Scand 160: 413-422.
82. Lin F, Wang R (2009). Molecular modeling of the three-dimensional structure of GLP-1R and its interactions with several agonists. J Mol Model 15: 53-65.
83. Liu HK, Green BD, Gault VA, McCluskey JT, McClenaghan NH, O'Harte FP et al. (2004). N-acetyl-GLP-1: a DPP IV-resistant analogue of glucagon-like peptide-1 (GLP-1) with improved effects on pancreatic [b]-cell-associated gene expression. Cell Biol Int 28: 69-73.
84. Lohse MJ, Engelhardt S, Eschenhagen T (2003). What Is the role of b-adrenergic signaling in heart failure? Circ Res 93: 896-906.
85. Lund PK, Goodman RH, Habener JF (1981). Intestinal glucagon mRNA identified by hybridization to a cloned islet cDNA encoding a precursor. Biochem Biophys Res Commun 100: 1659-1666.
86. Madsbad S, Schmitz O, Ranstam J, Jakobsen G, Matthews DR (2004). Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial. Diabetes Care 27: 1335-1342.
87. Martin B, Golden E, Carlson OD, Pistell P, Zhou J, Kim W et al. (2009). Exendin-4 improves glycemic control, ameliorates brain and pancreatic pathologies, and extends survival in a mouse model of Huntington's disease. Diabetes 58: 318-328.
88. Nauck MA, Wollschläger D, Werner J, Holst JJ, Orskov C, Creutzfeldt W et al. (1996). Effects of subcutaneous glucagon-like peptide 1 (GLP-1 [7-36 amide]) in patients with NIDDM. Diabetologia 39: 1546-1553.
89. Nauck M, Duran S, Kim D, Johns D, Northrup J, Festa A et al. (2007). A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabeto-logia 50: 259-267.
90. Nikolaidis LA, Elahi D, Hentosz T, Doverspike A, Huerbin R, Zourelias L et al. (2004a). Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomy-opathy. Circulation 110: 955-961.
91. Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D et al. (2004b). Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 109: 962-965.
92. Nikolaidis LA, Doverspike A, Hentosz T, Zourelias L, Shen YT, Elahi D et al. (2005a). Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines. J Pharmacol Exp Ther 312: 303-308.
93. Nikolaidis LA, Elahi D, Shen YT, Shannon RP (2005b). Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomy-opathy. Am J Physiol Heart Circ Physiol 289: H2401-H2408.
94. Nishizawa M, Nakabayashi H, Kawai K, Ito T, Kawakami S, Nakagawa A et al. (2000). The hepatic vagal reception of intraportal GLP-1 is via receptor different from the pancreatic GLP-1 receptor. J Auton Nerv Syst 80: 14-21.
95. Noyan-Ashraf MH, Momen MA, Ban K, Sadi AM, Zhou YQ, Riazi AM et al. (2009). GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes 58: 975-983.
96. Nystrom T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahren B et al. (2004). Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab 287: E1209-E1215.
97. Nystrom T, Gonon AT, Sjoholm A, Pernow J (2005). Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium-independent mechanism. Regul Pept 125: 173-177.
98. Orskov C, Poulsen SS (1991). Glucagon like peptide-I-(7-36)-amide receptors only in islets of Langerhans. Autoradiographic survey of extracerebral tissues in rats. Diabetes 40: 1292-1296.
99. Orskov C, Andreasen J, Holst JJ (1992). All products of proglucagon are elevated in plasma from uremic patients. J Clin Endocrinol Metab 74: 379-384.
100. Orskov C, Rabenhøj L, Wettergren A, Kofod H, Holst JJ (1994). Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans. Diabetes 43: 535-539.
101. Ozyazgan S, Kutluata N, Afsar S, Ozdas SB, Akkan AG (2005). Effect of glucagon-like peptide-1(7-36) and exendin-4 on the vascular reactivity in streptozotocin/nicotinamide-induced diabetic rats. Pharmacology 74: 119-126.
102. Perry TA, Greig NH (2004). A new Alzheimer's disease interventive strategy: GLP-1. Curr Drug Targets 5: 565-571.
103. Plamboeck A, Holst J, Carr R, Deacon C (2005). Neutral endopeptidase 24.11 and dipeptidyl peptidase IV are both mediators of the degradation of glucagon-like peptide 1 in the anaesthetised pig. Diabeto-logia 48: 1882-1890.
104. Poornima I, Brown S, Bhashyam S, Parikh P, Bolukoglu H, Shannon RP (2008). Chronic glucagon-like peptide-1 (GLP-1) infusion sustains LV systolic function and prolongs survival in the spontaneously hypertensive-heart failure prone rat. Circ Heart Fail 1: 153-160.
105. Ruiz-Grande C, Alarcón C, Castilla C, López Novoa JM, Villanueva-Peñacarrillo ML, Valverde I (1993). Renal catabolism of truncated glucagon-like peptide 1. Horm Metab Res 25: 612-616.
106. Sandhu H, Wiesenthal SR, MacDonald PE, McCall RH, Tchipashvili V, Rashid S et al. (1999). Glucagon-like peptide 1 increases insulin sensitivity in depancreatized dogs. Diabetes 48: 1045-1053.
107. Scandinavian Simvastatin Survival Study Group (1994). Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344: 1383-1389.
108. Schirra J, Katschinski M, Weidmann C, Schäfer T, Wank U, Arnold R et al. (1996). Gastric emptying and release of incretin hormones after glucose ingestion in humans. J Clin Invest 97: 92-103.
109. Shimizu I, Hirota M, Ohboshi C, Shima K (1987). Identification and localization of glucagon-like peptide-1 and its receptor in rat brain. Endocrinology 121: 1076-1082.
110. Sokos GG, Nikolaidis LA, Mankad S, Elahi D, Shannon RP (2006). Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail 12: 694-699.
111. Sokos GG, Bolukoglu H, German J, Hentosz T, Magovern J, Maher TD et al. (2007). Effect of glucagon-like peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting. Am J Cardiol 100: 824-829.
112. Sonne DP, Engstrom T, Treiman M (2008). Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia-reperfusion injury in rat heart. Regul Pept 146: 243-249.
113. Stoffel M, Espinosa R III, Le Beau MM, Bell GI (1993). Human glucagon-like peptide-1 receptor gene. Localization to chromosome band 6p21 by fluorescence in situ hybridization and linkage of a highly polymorphic simple tandem repeat DNA polymorphism to other markers on chromosome 6. Diabetes 42: 1215-1218.
114. Suzuki T, Oba K, Igari Y, Matsumura N, Watanabe K, Futami-Suda S et al. (2007). Colestimide lowers plasma glucose levels and increases plasma glucagon-like peptide-1(7-36) levels in patients with type 2 diabetes mellitus complicated by hypercholesterolemia. J Nippon Med Sch 74: 338-343.
115. The SOLVD Investigators (1992). Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327: 685-691.
116. Thiele TE, Van Dijk G, Campfield LA, Smith FJ, Burn P, Woods SC et al. (1997). Central infusion of GLP-1, but not leptin, produces conditioned taste aversions in rats. Am J Physiol Regul Integr Comp Physiol 272: R726-R730.
117. Thorens B (1992). Expression cloning of the pancreatic b cell receptor for the gluco-incretin hormone glucagon-like peptide 1. Proc Natl Acad Sci USA 89: 8641-8645.
118. Thorens B, Waeber G (1993). Glucagon-like peptide-I and the control of insulin secretion in the normal state and in NIDDM. Diabetes 42: 1219-1225.
119. Thorens B, Porret A, Bühler L, Deng SP, Morel P, Widmann C (1993). Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor. Diabetes 42: 1678-1682.
120. Thrainsdottir I, Malmberg K, Olsson A, Gutniak M, Rydén L (2004). Initial experience with GLP-1 treatment on metabolic control and myocardial function in patients with type 2 diabetes mellitus and heart failure. Diab Vasc Dis Res 1: 40-43.
121. Timmers L, Henriques JP, De Kleijn DP, Devries JH, Kemperman H, Steendijk P et al. (2009). Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol 53: 501-510.
122. Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CMB, Meeran K et al. (1996). A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 379: 69-72. (Pubitemid 26008136)
123. Uttenthal LO, Blazquez E (1990). Characterization of high-affinity receptors for truncated glucagon-like peptide-1 in rat gastric glands. FEBS Lett 262: 139-141.
124. Vila Petroff MG, Egan JM, Wang X, Sollott SJ (2001). Glucagon-like peptide-1 increases cAMP but fails to augment contraction in adult rat cardiac myocytes. Circ Res 89: 445-452.
125. Wei Y, Mojsov S (1995). Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett 358: 219-224.
126. White JW, Saunders GF (1986). Structure of the human ghicagon gene. Nucleic Acids Res 14: 4719-4730.
127. Willms B, Werner J, Holst JJ, Orskov C, Creutzfeldt W, Nauck MA (1996). Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2 (noninsulin-dependent) diabetic patients. J Clin Endocrinol Metab 81: 327-332.
128. Xiao Q, Giguere J, Parisien M, Jeng W, St-Pierre SA, Brubaker PL et al. (2001). Biological activities of glucagon-like peptide-1 analogues in vitro and in vivo. Biochemistry 40: 2860-2869.
129. Xie Y, Wang SX, Sha WW, Zhou X, Wang WL, Han LP et al. (2008). Effects and mechanism of glucagon-like peptide-1 on injury of rats cardiomyocytes induced by hypoxia-reoxygenation. Chin Med J 121: 2134-2138.
130. Yamamoto H, Lee CE, Marcus JN, Williams TD, Overton JM, Lopez ME et al. (2002). Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons. J Clin Invest 110: 43-52.
131. Yamamoto H, Kishi T, Lee CE, Choi BJ, Fang H, Hollenberg AN et al. (2003). Glucagon-like peptide-1-responsive catecholamine neurons in the area postrema link peripheral glucagon-like peptide-1 with central autonomic control sites. J Neurosci 23: 2939-2946.
132. Yu M, Moreno C, Hoagland KM, Dahly A, Ditter K, Mistry M et al. (2003). Antihypertensive effect of glucagon-like peptide 1 in Dahl salt-sensitive rats. J Hypertens 21: 1125-1135.
133. Zhao T, Parikh P, Bhashyam S, Bolukoglu H, Poornima IG, Shen YT et al. (2006). The direct effects of glucagon-like peptide-1 (GLP-1) on myocardial contractility and glucose uptake in normal and post-ischemic isolated rat hearts. J Pharmacol Exp Ther 317: 1106-1113.
134. Zinman B, Hoogwerf BJ, Milton DR, Giaconia JM, Kim DD, Trautmann ME et al. (2007). The effect of adding exenatide to a thiazolidinedi-one in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 146: 477-485.