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

F. P.M. O'Harte, Y. H.A. Abdel-Wahab, J. M. Conlon, P. R. Flatt

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


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 BRINBD11 cells. In acute (20 min) incubations, 10-9 mol/1 tGLP-1 enhanced insulin release by 2.2-fold and 1.5-fold at 5.6 and 11.1 mmol/1 glucose, respectively. In contrast, 10-9 mol/1 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/1-10-8 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/1 and 3 x 10-9 mol/1 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.

Original languageEnglish
Pages (from-to)1187-1193
Number of pages7
Issue number10
Publication statusPublished - 1998
Externally publishedYes


  • BRIN-BD11 cells
  • GLP-1(7-36)amide
  • Glycation
  • Insulin secretion

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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