Effect of Glucagon-Like peptide-1 (Proglucagon 78-107amide) on Hepatic Glucose Production in Healthy Man

Metabolism. 1994 Jan;43(1):104-8. doi: 10.1016/0026-0495(94)90164-3.

Abstract

The newly discovered intestinal hormone, glucagon-like peptide-1 (GLP-1) (proglucagon 78-107amide), stimulates insulin secretion and inhibits glucagon secretion in man and may therefore be anticipated to influence hepatic glucose production. To study this, we infused synthetic GLP-1 sequentially at rates of 25 and 75 pmol.kg-1.h-1 into eight healthy volunteers after an overnight fast and measured plasma concentrations of glucose, insulin, and glucagon and glucose turnover by a technique involving infusion of 3-3H-glucose. Plasma levels of GLP-1 increased by 21.3 +/- 3.1 and 75.4 +/- 3.2 pmol/L during the infusion, changes that were within physiologic limits. In a control experiment only saline was infused. During GLP-1 infusion, plasma glucose level decreased significantly (from 5.3 +/- 0.1 to 4.7 +/- 0.1 and 4.3 +/- 0.1 pmol/L at the end of the two infusion periods). Despite this, plasma insulin level increased significantly (from 20.5 +/- 2.9 to a peak value of 33.5 +/- 5.2 pmol/L during the second period), and plasma glucagon level decreased (from 9.3 +/- 1.7 to 7.1 +/- 1.0 pmol/L). Glucose rate of appearance (Ra) decreased significantly to 75% +/- 6% of the preinfusion values during GLP-1 infusion. Glucose disappearance rate (Rd) did not change significantly, but glucose clearance increased significantly compared with saline. All parameters of glucose turnover remained constant during saline infusion. We conclude that GLP-1 may potently control hepatic glucose production and glucose clearance through its effects on the pancreatic glucoregulatory hormones. The effect of GLP-1 on glucose production is consistent with its proposed use in the treatment of type II diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Glucagon / blood
  • Glucagon / metabolism
  • Glucagon / pharmacology*
  • Glucagon-Like Peptide 1
  • Glucose / metabolism*
  • Humans
  • Insulin / blood
  • Insulin / metabolism
  • Liver / metabolism*
  • Male
  • Peptide Fragments / blood
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Protein Precursors / blood
  • Protein Precursors / metabolism
  • Protein Precursors / pharmacology*
  • Radioimmunoassay

Substances

  • Blood Glucose
  • Insulin
  • Peptide Fragments
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon
  • Glucose