Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus

J Clin Invest. 1993 Jan;91(1):301-7. doi: 10.1172/JCI116186.

Abstract

In type-2 diabetes, the overall incretin effect is reduced. The present investigation was designed to compare insulinotropic actions of exogenous incretin hormones (gastric inhibitory peptide [GIP] and glucagon-like peptide 1 [GLP-1] [7-36 amide]) in nine type-2 diabetic patients (fasting plasma glucose 7.8 mmol/liter; hemoglobin A1c 6.3 +/- 0.6%) and in nine age- and weight-matched normal subjects. Synthetic human GIP (0.8 and 2.4 pmol/kg.min over 1 h each), GLP-1 [7-36 amide] (0.4 and 1.2 pmol/kg.min over 1 h each), and placebo were administered under hyperglycemic clamp conditions (8.75 mmol/liter) in separate experiments. Plasma GIP and GLP-1 [7-36 amide] concentrations (radioimmunoassay) were comparable to those after oral glucose with the low, and clearly supraphysiological with the high infusion rates. Both GIP and GLP-1 [7-36 amide] dose-dependently augmented insulin secretion (insulin, C-peptide) in both groups (P < 0.05). With GIP, the maximum effect in type-2 diabetic patients was significantly lower (by 54%; P < 0.05) than in normal subjects. With GLP-1 [7-36 amide] type-2 diabetic patients reached 71% of the increments in C-peptide of normal subjects (difference not significant). Glucagon was lowered during hyperglycemic clamps in normal subjects, but not in type-2 diabetic patients, and further by GLP-1 [7-36 amide] in both groups (P < 0.05), but not by GIP. In conclusion, in mild type-2 diabetes, GLP-1 [7-36 amide], in contrast to GIP, retains much of its insulinotropic activity. It also lowers glucagon concentrations.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Female
  • Gastric Inhibitory Polypeptide / blood*
  • Gastric Inhibitory Polypeptide / pharmacology*
  • Glucagon / blood*
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Glucose Clamp Technique
  • Glycated Hemoglobin A / analysis
  • Humans
  • Insulin / blood*
  • Insulin / metabolism
  • Insulin Secretion
  • Kinetics
  • Male
  • Middle Aged
  • Peptide Fragments / blood*
  • Peptide Fragments / pharmacology*
  • Protein Precursors / blood*
  • Reference Values
  • Time Factors

Substances

  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Insulin
  • Peptide Fragments
  • Protein Precursors
  • glucagon-like peptide 1 (7-36)amide
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon