Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes

Diabetes. 2000 Apr;49(4):611-7. doi: 10.2337/diabetes.49.4.611.

Abstract

Although it is well established that glucagon-like peptide 1(7-36) amide (GLP-1) is a potent stimulator of insulin secretion, its effects on insulin action and glucose effectiveness are less clear. To determine whether GLP-1 increases insulin action and glucose effectiveness, subjects with type 2 diabetes were studied on two occasions. Insulin was infused during the night on both occasions to ensure that baseline glucose concentrations were comparable. On the morning of study, either GLP-1 (1.2 pmol x kg(-1) x min(-1)) or saline were infused along with somatostatin and replacement amounts of glucagon. Glucose also was infused in a pattern mimicking that typically observed after a carbohydrate meal. Insulin concentrations were either kept constant at basal levels (n = 6) or varied so as to create a prandial insulin profile (n = 6). The increase in glucose concentration was virtually identical on the GLP-1 and saline study days during both the basal (1.21 +/- 0.15 vs. 1.32 +/- 0.19 mol/l per 6 h) and prandial (0.56 +/- 0.14 vs. 0.56 +/- 0.10 mol/l per 6 h) insulin infusions. During both the basal and prandial insulin infusions, glucose disappearance promptly increased after initiation of the glucose infusion to rates that did not differ on the GLP-1 and saline study days. Suppression of endogenous glucose production also was comparable on the GLP-1 and saline study days during both the basal (-2.7 +/- 0.3 vs. -3.1 +/- 0.2 micromol/kg) and prandial (-3.1 +/- 0.4 vs. -3.0 +/- 0.6 pmol/kg) insulin infusions. We conclude that when insulin and glucagon concentrations are matched, GLP-1 has negligible effects on either insulin action or glucose effectiveness in people with type 2 diabetes. These data strongly support the concept that GLP-1 improves glycemic control in people with type 2 diabetes by increasing insulin secretion, by inhibiting glucagon secretion, and by delaying gastric emptying rather than by altering extrapancreatic glucose metabolism.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blood Glucose / metabolism*
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Food
  • Gastric Emptying / drug effects
  • Glucagon / administration & dosage
  • Glucagon / blood
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Human Growth Hormone / blood
  • Humans
  • Hydrocortisone / blood
  • Insulin / administration & dosage
  • Insulin / blood
  • Insulin / therapeutic use*
  • Kinetics
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / therapeutic use
  • Somatostatin

Substances

  • Blood Glucose
  • C-Peptide
  • Insulin
  • Peptide Fragments
  • glucagon-like peptide 1 (7-36)amide
  • Human Growth Hormone
  • Somatostatin
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon
  • Hydrocortisone