Effects of secretagogues on insulin biosynthesis and secretion in polyamine-depleted pancreatic beta-cells.
To extend previous observations on the importance of polyamines for glucose-stimulated insulinogenesis (N. Welsh and A Sjöholm. Polyamines and insulin production in isolated mouse pancreatic islets. Biochem. J. 252: 701-707, 1988), the impact of other secretagogues on insulin secretion of islets partially depleted in polyamines by selective inhibitors of L-ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase 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 islets were stimulated with nonglucidic nutrients (alpha-ketoisocaproic acid + L-glutamine), a cationic amino acid (L-arginine), activators of phospholipase C (carbachol) or protein kinase C (12-O-tetradecanoylphorbol 13-acetate), an adenosine 1', 5'-cyclic monophosphate-raising agent (forskolin), or a hypoglycemic sulfonylurea (glibenclamide). Additionally, 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 release. 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.
Sjöholm
A
A
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
D012437:Adenosylmethionine Decarboxylase / Q000494:pharmacology*; D000480:Alkynes; D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism*; D003959:Diamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D000480:Alkynes; D015317:Biogenic Polyamines; D003959:Diamines; D004791:Enzyme Inhibitors; D007328:Insulin; C039613:6-heptyne-2,5-diamine; D012437:Adenosylmethionine Decarboxylase; D005947:Glucose; D000518:Eflornithine