Amino terminal glycation of gastric inhibitory polypeptide enhances its insulinotropic action on clonal pancreatic B-cells.

Gastric inhibitory polypeptide (GIP) is a potent insulin-releasing hormone of the enteroinsular axis. This study has examined glycation of GIP and effects of such structural modification on insulin secretion from a glucose-responsive clonal pancreatic B-cell line (BRIN-BD11). Monoglycated GIP (Mr 5149.5) was prepared by incubation with d-glucose under reducing conditions and purified by HPLC. Automated Edman degradation and mass spectrometric analysis indicated that GIP was specifically glycated at the amino terminus. In acute (20 min) incubations at 5.6 mM glucose, GIP (3x10-11-10-8 M) significantly stimulated insulin secretion by 1.6-2.1-fold from BRIN-BD11 cells. The stimulatory effect induced by GIP over this concentration range was further enhanced by 1.5-2.5-fold following N-terminal glycation. These data indicate that GIP can be glycated under hyperglycaemic conditions at the amino terminal Tyr1, and that this modification increases the glucose-dependent insulinotropic action of the peptide.