Effect of glucagon-like peptide-1(7-36) and exendin-4 on the vascular reactivity in streptozotocin/nicotinamide-induced diabetic rats

Abstract

We investigated the vascular effects of glucagon-like peptide-1 (GLP-1) and Exendin-4 in type 2 diabetic rat aortae. Studies were performed in a normal control group (NC) (0.2 ml i. p. saline, n = 10), streptozotocin (STZ)/ nicotinamide diabetic control group ( DC) ( a single dose of 80 mg/kg STZ i. p. injection 15 min after administration of 230 mg/kg nicotinamide i. p.), GLP-1 (GLPC) control group ( 1 mu g/kg twice daily i. p. for 1 month, n = 10), Exendin-4 control group (EXC) ( 0.1 mu g/kg twice daily i. p. for 1 month, n = 10), GLP-1-treated diabetic group (GLPT) ( 1 mu g/kg twice daily i. p. for 1 month, n = 10), and Exendin-4-treated diabetic group (EXT) ( 0.1 mu g/kg twice daily i. p. for 1 month, n = 10). One month of GLP-1 and Exendin-4 treatment significantly decreased the blood glucose levels of diabetic rats ( 113 +/- 2 mg/dl, p < 0.001, and 117 +/- 1 mg/ dl, p < 0.001, respectively versus 181 +/- 9 mg/ dl in the DC group). Sensitivity (pD(2)) and maximum response (% Max. Relax) of acetylcholine-stimulated relaxations in the DC group (pD(2) : 6.73 +/- 0.12 and 55 +/- 6, respectively) were decreased compared with the nondiabetic NC group (pD(2) : 7.41 +/- 0.25, p < 0.05, and 87 +/- 4, p < 0.01). Treating diabetic rats with GLP-1, pD(2) values and with Exendin-4, Max. Relax % values of aortic strips to acetylcholine returned to near non-diabetic NC values (pD(2) : 7.47 +/- 0.15, p < 0.05, and 87 +/- 3, p < 0.01, respectively). Maximal contractile responses (E-max) to noradrenaline in aortic strips from the diabetic DC group (341 +/- 27 mg tension/mg wet weight) were significantly decreased compared with the non-diabetic NC ( 540 +/- 66 mg tension/mg wet weight, p < 0.001) and the GLPT group ( 490 +/- 25 mg tension/ mg wet weight, p < 0.05). There were no significant differences in pD(2) values of aortic strips to noradrenaline from all groups. E-max to KCl in aortic strips from the DC group ( 247 +/- 10 mg tension/ mg wet weight, p < 0.01) was significantly decreased compared with non-diabetic NC group ( 327 +/- 26 mg tension/ mg wet weight). Treating diabetic rats with GLP-1 (GLPT), E-max values of aortic strips to KCl returned to near non-diabetic NC values ( 271 +/- 12 mg tension/ mg wet weight). GLP-1 and ( partially) Exendin-4 treatment could improve the increased blood glucose level and normalize the altered vascular tone in type 2 diabetic rats. Copyright (C) 2005 S. Karger AG, Basel.