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

Pharmacology. 2005 Jun;74(3):119-26. doi: 10.1159/000084277. Epub 2005 Mar 3.

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 microg/kg twice daily i.p. for 1 month, n = 10), Exendin-4 control group (EXC) (0.1 microg/kg twice daily i.p. for 1 month, n = 10), GLP-1-treated diabetic group (GLPT) (1 microg/kg twice daily i.p. for 1 month, n = 10), and Exendin-4-treated diabetic group (EXT) (0.1 microg/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 (pD2) and maximum response (% Max. Relax) of acetylcholine-stimulated relaxations in the DC group (pD2: 6.73 +/- 0.12 and 55 +/- 6, respectively) were decreased compared with the non-diabetic NC group (pD2: 7.41 +/- 0.25, p < 0.05, and 87 +/- 4, p < 0.01). Treating diabetic rats with GLP-1, pD2 values and with Exendin-4, Max. Relax %values of aortic strips to acetylcholine returned to near non-diabetic NC values (pD2: 7.47 +/- 0.15, p < 0.05, and 87 +/- 3, p < 0.01, respectively). Maximal contractile responses (Emax) 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 pD2 values of aortic strips to noradrenaline from all groups. Emax 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), Emax 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Dose-Response Relationship, Drug
  • Exenatide
  • Female
  • Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • In Vitro Techniques
  • Male
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Niacinamide
  • Oxidative Stress / drug effects
  • Peptide Fragments / pharmacology*
  • Peptides / pharmacology*
  • Rats
  • Rats, Wistar
  • Streptozocin
  • Vasodilator Agents / pharmacology*
  • Venoms / pharmacology*

Substances

  • Blood Glucose
  • Peptide Fragments
  • Peptides
  • Vasodilator Agents
  • Venoms
  • glucagon-like peptide 1 (7-36)
  • Niacinamide
  • Streptozocin
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon
  • Exenatide