Glucagon-like peptide-1 augments insulin-mediated glucose uptake in the obese state

J Clin Endocrinol Metab. 2002 Aug;87(8):3768-73. doi: 10.1210/jcem.87.8.8743.


The insulinotropic hormone, glucagon-like peptide-1 (GLP-1), is being examined as a potential new agent for treatment in type 2 diabetic patients. Whereas the insulinotropic properties of this peptide are well established, another property of the hormone, an insulinomimetic effect per se, is controversial. In the normal glucose-tolerant lean state, it is difficult to demonstrate an insulinomimetic effect. The current study was conducted to examine whether GLP-1 has insulinomimetic effect in the obese state. Ten obese volunteers (body mass index, 34.6 +/- 0.8 kg/m(2)), whose ages were 32.5 +/- 3.0 yr, participated in two euglycemic clamp studies (n = 20 clamps) for 120 min. Five of the volunteers were females. The initial clamp was performed with a primed (0-10)-constant (10-60) infusion of GLP-1 at a final rate of 1.5 pmol x kg(-1) x min(-1). At 60 min, the GLP-1 infusion was terminated, and euglycemic was maintained from 60-120 min. After the GLP-1 study, each individual's plasma insulin level was measured. A second study was performed that was identical to the first, with the infusion of regular insulin in place of GLP-1. Insulin infusion rates were regulated in each individual to simulate plasma insulin levels produced during the GLP-1 infusion. The rate of disappearance of glucose was calculated for each subject. Fasting plasma insulin levels were similar between studies. In response to the GLP-1 infusion, with maintenance of plasma glucose level clamped at fasting level, significant increases in plasma insulin occurred in all subjects (P < 0.001). The insulin levels during the insulin infusion study were similar to that induced by GLP-1. The rate of disappearance of glucose (insulin-mediated glucose uptake) progressively increased in response to both the GLP-1 and insulin infusion. However, the rate of disappearance of glucose during the GLP-1 study was significantly higher (P = 0.033) than during the insulin study. We conclude that in insulin-resistant states, GLP-1 has insulinomimetic properties per se.

Publication types

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

MeSH terms

  • Adult
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Therapy, Combination
  • Fatty Acids, Nonesterified / blood
  • Female
  • Glucagon / administration & dosage*
  • Glucagon / blood
  • Glucagon-Like Peptide 1
  • Glucose / pharmacokinetics
  • Glucose Clamp Technique
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / blood
  • Insulin / administration & dosage*
  • Insulin / blood
  • Insulin Resistance
  • Male
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Peptide Fragments / administration & dosage*
  • Protein Precursors / administration & dosage*


  • Blood Glucose
  • C-Peptide
  • Fatty Acids, Nonesterified
  • Hypoglycemic Agents
  • Insulin
  • Peptide Fragments
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon
  • Glucose