2001 Volume 4 Issue 2 Pages 101-109
Mastoparan(MP, INLKALAALAKKIL-NH_2)is a potent stimulator of exocytosis, including the process of insulin secretion. To examine the insulinotropic effect of MP in pancreatic β-cells, we measured insulin release from isolated rat islets. MP enhanced insulin release, irrespective of the presence or absence of glucose. This enhancement was observed under a stringent extracellular Ca^<2+> -free condition and also in the presence of diazoxide, a K_<ATP> channel opener. These results suggest that K_<ATP> channel closure, which is a key step in glucose-stimulated insulin secretion, is not necessarily involved in MP-induced insulin secretion. The effect of MP on both cAMP and protein kinase pathways was also studied. MP had no effects on the elevation of intracellular cAMP content, whereas staurosporine, a PKA and PKC inhibitor, attenuated MP-stimulated insulin secretion. These suggested that the activation of PKC in β-cells is involved in MP-stimulated insulin secretion. This effect on PKC seemed to be due to the rise of intracellular Ca^<2+>. MP is known to induce the activation of phospholipase C(PLC)and the production of inositol 1, 4, 5-triphosphate(IP3), which mediates Ca^<2+> release from intracellular stores. These observations strongly suggested that MP might induce Ca^<2+> release from intracellular store, probably via activation of PLC and IP3, thereby stimulating exocytosis from the insulin secretory granules of pancreatic islets.
