Glucagon-like peptide-1(1-37) can enhance blood glucose homeostasis in mice

Regul Pept. 2012 Oct 10;178(1-3):1-5. doi: 10.1016/j.regpep.2012.06.010. Epub 2012 Jun 29.

Abstract

Glucagon-like peptide-1 (GLP-1) is produced by the posttranslational processing of proglucagon and acts as a regulator of various homeostatic events. No blood glucose regulation role of GLP-1(1-37) has previously been identified. However, our findings in this study clearly showed that GLP-1(1-37) could lower blood glucose levels both in normal and diabetic mice. In vitro stability analysis demonstrated that GLP-1(1-37) was more stable than GLP-1(7-37), with 94.7% of the initial amount of peptide left after a 4h exposure to mouse serum. Moreover, GLP-1(1-37) was confirmed to be a highly potent agonist of the GLP-1 receptor (GLP-1R) by measuring the expression of the luciferase reporter gene expression in transiently transfected human embryonic kidney (HEK293) cells. Unlike the glucose lowering effect of GLP-1(7-37), the glucose-lowering effect of GLP-1(1-37) could not be blocked by the GLP-1R antagonist exendin(9-39), suggesting that GLP-1(1-37) might activate the GLP-1R via a different mechanism. Therefore, our findings suggest that GLP-1(1-37) could be a potential therapeutic drug for the treatment of type 2 diabetes in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Area Under Curve
  • Blood Glucose*
  • Drug Stability
  • Escherichia coli
  • Female
  • Genes, Reporter
  • Glucagon-Like Peptide 1 / administration & dosage*
  • Glucagon-Like Peptide 1 / biosynthesis
  • Glucagon-Like Peptide 1 / isolation & purification
  • Glucagon-Like Peptide-1 Receptor
  • Glucose Tolerance Test
  • HEK293 Cells
  • Homeostasis*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / metabolism
  • Luciferases / biosynthesis
  • Luciferases / genetics
  • Mice
  • Peptide Fragments / administration & dosage
  • Receptors, Glucagon / agonists
  • Receptors, Glucagon / metabolism
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification

Substances

  • Blood Glucose
  • GLP1R protein, human
  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Peptide Fragments
  • Receptors, Glucagon
  • Recombinant Proteins
  • exendin (9-39)
  • Glucagon-Like Peptide 1
  • Luciferases