GIP regulates glucose transporters, hexokinases, and glucose-induced insulin secretion in RIN 1046-38 cells.

Acute studies of glucose-dependent insulinotropic peptide (GIP) have shown that GIP can synergize with glucose in stimulating insulin secretion 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 stimulating insulin secretion. Incubation of the cells with 100 nM GIP in the presence of glucose for 12 h significantly increased insulin release (287 +/- 31.7 vs. 102 +/- 9.7 ng/mg protein; n = 3), intracellular insulin content (12.8 +/- 0.83 vs. 8.2 +/- 0.52 ng/mg protein; n = 3), and insulin 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-1 and hexokinase I mRNA (1.75-fold) compared to non-GIP-treated cells; mRNA levels of GLUT-2 and glucokinase were unchanged by GIP, in the presence or absence of glucose. Our study suggests that the mechanism by which extended exposure of RIN 1046-38 cells to GIP increases glucose-stimulated insulin secretion includes up-regulation of glucose sensing elements.