Mastoparan stimulates insulin secretion from pancreatic beta-cells by effects at a late stage in the secretory pathway.
Mastoparan (MP) is a component of wasp venom which stimulates secretion from a number of cell types. We have used intact and electrically permeabilised islets of Langerhans to investigate the mechanisms through which MP stimulates insulin secretion from pancreatic beta-cells. MP caused a temperature-dependent and dose-related stimulation of insulin secretion from intact islets at a substimulatory concentration (2 mM) of glucose, which was not dependent upon the presence of extracellular Ca2+. MP also stimulated ATP-independent insulin secretion from electrically permeabilised islets in which intracellular Ca2+ was clamped at a substimulatory concentration (50 nM). MP-induced insulin secretion was not inhibited by down-regulation of islet protein kinase C, nor by the protein kinase inhibitor staurosporine, nor by the cyclic AMP antagonist Rp-adenosine 3',5'-cyclic phosphorothioate. However, MP-induced secretion from permeabilised islets was inhibited by the presence of guanosine 5'-O-2-thiodiphosphate. These results suggest that MP stimulates insulin secretion by a mechanism that is independent of changes in cytosolic Ca2+ or protein kinase activation, but which is dependent, at least in part, upon activation of a GTP-binding protein at a late stage in the secretory process.
Biomedical Sciences Division, King's College London, Kensington, UK.
P M
PM
Jones
F M
FM
Mann
S J
SJ
Persaud
C P
CP
Wheeler-Jones
D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002463:Cell Membrane Permeability; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D036341:Intercellular Signaling Peptides and Proteins; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology*
D000470:Alkaloids; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; D014862:Wasp Venoms; D006153:Guanosine Diphosphate; C016957:adenosine-3',5'-cyclic phosphorothioate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C023427:guanosine 5'-O-(2-thiodiphosphate); C037500:mastoparan; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D019311:Staurosporine; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium