GIP REGULATES GLUCOSE TRANSPORTERS, HEXOKINASES, AND GLUCOSE-INDUCED INSULIN-SECRETION IN RIN-1046-38 CELLS

Acute studies of glucose-dependent insulinotropic peptide (GIP) have s hown that GIP can synergize with glucose in stimulating insulin secret ion both in vivo and in vitro. Here we studied the effects of extended exposure of RIN 1046-38 cells, an insulin-secreting cell line, to GIP and the mechanisms by which GIP synergizes with glucose in stimulatin g insulin secretion. Incubation of the cells with 100 nM GIP in the pr esence of glucose for 12 h significantly increased insulin release (28 7 +/- 31.7 vs. 102 +/- 9.7 ng/mg protein; n = 3), intracellular insuli n content (12.8 +/- 0.83 vs. 8.2 +/- 0.52 ng/mg protein; n = 3), and i nsulin mRNA (approximately 2.7-fold; 24 h incubation) when compared to cells cultured with glucose alone. The insulinotropic effects of GIP on RIN 1046-38 cells were accompanied by an up-regulation of GLUT-I an d hexokinase I mRNA (1.75-fold) compared to non-GIP-treated cells; mRN A levels of GLUT-2 and glucokinase were unchanged by GIP, in the prese nce or absence of glucose. Our study suggests that the mechanism by wh ich extended exposure of RIN 1046-38 cells to GIP increases glucose-st imulated insulin secretion includes up-regulation of glucose sensing e lements.