Abstract
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 language | English |
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Pages (from-to) | 1187-1193 |
Number of pages | 7 |
Journal | Diabetologia |
Volume | 41 |
Issue number | 10 |
DOIs | |
Publication status | Published - 1998 |
Externally published | Yes |
Keywords
- BRIN-BD11 cells
- GLP-1(7-36)amide
- Glycation
- Insulin secretion
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism