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1 Department of Endocrinology, Mayo Clinic, Rochester, Minnesota, United States
2 Physiology & Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, United States
3 Rochester, Minnesota, United States; Physiology & Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, United States
4 Endocrinology Department, Mayo Clinic, Rochester, Minnesota, United States; Department of Endocrinology, Mayo Clinic, Rochester, Minnesota, United States
5 Rochester, Minnesota, United States; Department of Endocrinology, Mayo Clinic, Rochester, Minnesota, United States
6 Anesthesiology, Mayo Clinic & Foundation, Rochester, Minnesota, United States
* To whom correspondence should be addressed. E-mail: basu.ananda{at}mayo.edu.
Sulphonylureas (SU) with Glucagon-like peptide-1 (GLP-1) based therapy are an emerging therapeutic combination for type 2 diabetes. Prior human studies have hinted at endothelial effects of GLP-1 and SU. To study the endothelial effects of GLP-1 per se and to evaluate the modulatory effects, if any, of SU agents on GLP-1 induced changes in endothelial function, healthy nondiabetic, normotensive, nonsmokers, age 18-50 years with no family history of diabetes were studied. Subjects were randomized to either placebo (n=10), glyburide 10 mg (n=11) or glimepiride 4 mg (n=8) orally. Euglycemic somatostatin pancreatic clamp with replacement basal insulin, glucagon and growth hormone was performed for 240 min. Forearm blood flow (FBF) was measured by venous occlusion plethysmography with graded brachial artery infusions of acetylcholine (Ach) and nitroprusside (NTP) before and after intravenous infusion of GLP-1. GLP-1 (pre-infusion 3.4±0.2, post-infusion 25.5±2.8 pM) enhanced (p<0.03) Ach mediated vasodilatation (
+6.5±1.1 vs. +9.1±1.2 ml/100 ml/min, change from baseline FBF) in those on placebo. However, in contrast, glyburide abolished GLP-1 induced Ach mediated vasodilatation (+11.7±2.0 vs. +11.7±2.5 ml/100 ml/min). On the other hand, glimepiride did not alter the ability of GLP-1 to enhance Ach mediated vasodilatation (+7.9±0.5 vs. +10.2±1.3 ml/100 ml/min; p< 0.04). Neither GLP-1, nor SU altered NTP induced vasodilatation. These data demonstrate that GLP-1 per se has direct beneficial effects on endothelium dependent vasodilatation in humans that is differentially modulated by sulphonylureas.
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