Glucose activates prenyltransferases in pancreatic islet beta-cells

A growing body of evidence implicates small G-proteins [e.g, Cdc42 and Rac1] in glucose-stimulated insulin secretion [GSIS] in the islet beta-cell. These signaling proteins undergo post-translational modifications [e g, prenylation] at their C-terminal cysteine residue and appear to be essential for the transport and fusion of insulin-containing secretary granules with the plasma membrane and the exocytotic secretion of insulin. However, potential regulation of the prenylating enzymes by physiological Insulin secretogues [e.g. glucose] has not been investigated thus far. Herein. we report immunological localization. sub-cellular distribution and regulation of farnesyltransferases [FTases] and geranylgeranyltransferase [GGTase] by glucose in insulin-secreting INS 832/13 beta-cells and normal rat islets Our findings suggest that an insulinotropic concentration of glucose [20 mM] markedly stimulated the expression of the alpha-subunits of FTase/GGTase-1. but not the beta-subunits of FTase or GGTase-1 without significantly affecting the predominantly cytosolic distribution of these holoenzymes in INS 832/13 cells and rodent islets Under these conditions, glucose significantly stimulated [2.5- to 4.0-fold over basal] the activities of both FTase and GGTase-1 in both cell types. Together, these findings provide the first evidence to Suggest that GSIS involves activation of the endogenous islet prenyltransferases by glucose, Culminating in the activation of their respective G-protein substrates, which is necessary for cytoskeletal rearrangement, vesicular transport, fusion and secretion of insulin Published by Elsevier Inc