Characterization of GIP(1-30) and GIP(1-42) as stimulators of proinsulin gene transcription.
Originally characterized in terms of its gastric acid inhibitory properties, GIP (gastric inhibitory polypeptide) expressed in the upper small intestine, was subsequently shown to exert strong glucose-dependent insulin-releasing properties. This action is generally attributed to GIP(1-42) and, so far, no evidence for the contribution of other relevant GIP forms exists. In this study, we compared the effects of GIP(1-42) and C-terminally truncated GIP(1-30) on cAMP production and proinsulin gene transcription at clonal insulin-secreting cell lines (RIN 1046-38, beta TC-3). Both peptides were equally potent stimulators of cAMP generation in both cell lines. Insulin release from RIN 1046-38 cells stimulated by both GIP forms was identical. In both B-cell lines GIP(1-42) and GIP(1-30) stimulated proinsulin gene expression equipotently. GIP not only enhances insulin secretion but also insulin gene expression and, therefore, it is a true insulinotropic hormone.
Department of Medicine, Philipps-University of Marburg, Germany.
H C
HC
Fehmann
B
B
Göke
D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011384:Proinsulin / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
D007328:Insulin; D010446:Peptide Fragments; D005749:Gastric Inhibitory Polypeptide; D011384:Proinsulin; D000242:Cyclic AMP