Glycation of glucagon-like peptide-1(7-36)amide: characterization and impaired action on rat insulin secreting cells

Diabetologia. 1998 Oct;41(10):1187-93. doi: 10.1007/s001250051050.


Glucagon-like peptide-1(7-36)amide(truncated GLP-1, tGLP-1) is a potent insulin releasing hormone of the enteroinsular axis. This study has examined glycation of tGLP-1 and effects of such structural modification on insulin secretion. Monoglycated tGLP-1 (M(r) 3463.8, determined by plasma desorption mass spectrometry) was prepared by incubation with glucose under reducing conditions and purified by reversed-phase high performance liquid chromatography. Automated Edman degradation indicated that tGLP-1 was specifically glycated at the amino terminal His7 site. In extracts from mouse small intestine, glycated tGLP-1 represented approximately 14% of the total tGLP-1 content. Effects of glycated and non-glycated tGLP-1 on insulin secretion were examined using glucose-responsive clonal BRIN-BD11 cells. In acute (20 min) incubations, 10(-9) mol/l tGLP-1 enhanced insulin release by 2.2-fold and 1.5-fold at 5.6 and 11.1 mmol/l glucose, respectively. In contrast, 10(-9) mol/l glycated tGLP-1 failed to stimulate secretion and insulin output was decreased by 34-73% following glycation. At 5.6 mmol/l glucose, non-glycated tGLP-1 (3 x 10(-10) mol/l-10(-8) mol/l) exerted a 2.3-fold to 3.2-fold increase in insulin secretion compared with controls. The effect of glycated tGLP-1 at 10(-9) mol/l and 3 x 10(-9) mol/l was reduced by 51-55% compared with non-glycated peptide, and its insulinotropic action was effectively abolished. These data indicate that when tGLP-1 is glycated at the amino terminal His7, this modification substantially reduces the glucose-dependent insulinotropic action of the peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibody Specificity
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Glycosylation
  • Insulin / metabolism*
  • Insulin Secretion
  • Intestine, Small / chemistry
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Mice
  • Molecular Sequence Data
  • Peptide Fragments / analysis
  • Peptide Fragments / chemistry*
  • Peptide Fragments / pharmacology*
  • Radioimmunoassay
  • Rats
  • Sequence Analysis
  • Structure-Activity Relationship


  • Insulin
  • Peptide Fragments
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon