Glucagon-like peptide-1 has no insulin-like effects in insulin-dependent diabetic dogs maintained normoglycemic and normoinsulinemic

Abstract

A pharmacological concentration of glucagon-like peptide-1 (GLP-1) in the insulin-deficient state clearly decreases the blood glucose level. Therefore, this study was designed to evaluate a putatively relevant effect of the gastrointestinal peptide as an adjuvant to insulin replacement therapy. GLP-1 (GLP-1(7–36) amide 10 pmol · kg −1 · min −1) was infused intravenously over 8 hours in nine fasting, C-peptide-negative diabetic dogs. The animals were under normoglycemic control by glucose-controlled insulin infusion (GCII) during the night before and during GLP-1 administration. During the paired control tests, the animals received saline infusion instead of GLP-1. In addition to the insulin infusion rates required to maintain normoglycemia, hormones, metabolites, and the turnover rates for glucose (6- 3H-glucose), alanine (U- 14C-alanine), and urea ( 15N 2-urea) were measured during the final 2 hours of GLP-1 administration. Circulating plasma GLP-1 levels increased from 3 ± 1 to 17 ± 7 pmol/L. There was no significant difference in the insulin infusion rate between the experimental and control groups (0.43 ± 0.05 v 0.40 ± 0.05 mU · kg −1 · h −1, average over the entire interval). Glycemia was maintained at a practically identical level (4.9 ± 0.3 v 4.8 ± 0.4 mmol/L). Also, the concentration of plasma insulin—which was not hyperinsulinemic—and pancreatic glucagon remained unaltered. We found no appreciable effect of GLP-1 on glucose production and metabolic clearance, alanine turnover and the formation of glucose from alanine (1.8 ± 0.2 v 1.4 ± 0.2 μmol · kg −1 · min −1), or the urea production rate as a measure of overall amino acid catabolism (4.1 ± 0.4 v 4.1 ± 0.4 μmol · kg −1 · min −1). Thus, no conclusive adjuvant effect of GLP-1 was ascertained in insulin-treated diabetic dogs under normoglycemic control.