EFFECTS OF SECRETAGOGUES ON INSULIN-BIOSYNTHESIS AND SECRETION IN POLYAMINE-DEPLETED PANCREATIC BETA-CELLS

To extend previous observations on the importance of polyamines for gl ucose-stimulated insulinogenesis (N. Welsh and A. Sjoholm. Polyamines and insulin production in isolated mouse pancreatic islets. Biochem. J . 252: 701-707, 1988), the impact of other secretagogues on insulin se cretion of islets partially depleted in polyamines by selective inhibi tors of L-ornithine decarboxylase and S-adenosyl-L-methionine decarbox ylase was monitored. Glucose-sensitive, but not basal, insulin release was partially abolished in polyamine-deficient islets. Qualitatively similar impairments in insulin secretion were recorded when such islet s were stimulated with nonglucidic nutrients (alpha-ketoisocaproic aci d + L-glutamine), a cationic amino acid (L-arginine), activators of ph ospholipase C (carbachol) or protein kinase C (12-O-tetradecanoylphorb ol 13-acetate), an adenosine 3',5',-cyclic monophosphate-raising agent (forskolin), or a hypoglycemic sulfonylurea (glibenclamide). Addition ally, glucose-responsive (pro)insulin biosynthesis was preferentially impeded in polyamine-deficient islets. It is concluded that polyamines act as permissive or stimulatory factors in insulin production and re lease. In addition, they seemingly do not act in an inhibitory manner on phospholipase C, protein kinase C, or Ca2+ flux into these islets, in contrast to reports in which insulinoma and other cells were used.