Dissociation between changes in cytoplasmic free Ca2+ concentration and insulin secretion as evidenced from measurements in mouse single pancreatic islets.
Simultaneous measurements of cytosolic free Ca2+ concentration and insulin release, in mouse single pancreatic islets, revealed a direct correlation only initially after stimulation with glucose or K+. Later, there is an apparent dissociation between these two parameters, with translocation of alpha and epsilon isoenzymes of protein kinase C to membranes and simultaneous desensitization of insulin release in response to glucose. Recovery of insulin release, without any concomitant changes in cytosolic free Ca2+ concentration, after addition of phorbol 12-myristate 13-acetate, okadaic acid, and forskolin supports the notion that the desensitization process is accounted for by dephosphorylation of key regulatory sites of the insulin exocytotic machinery.
Zaitsev
S V
SV
Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Efendić
S
S
Arkhammar
P
P
Bertorello
A M
AM
Berggren
P O
PO
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation; D005576:Colforsin / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007527:Isoenzymes / Q000032:analysis; D008566:Membranes / Q000201:enzymology; D051379:Mice; D008820:Mice, Obese; D019319:Okadaic Acid; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000032:analysis; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D011863:Radioimmunoassay; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D007328:Insulin; D007527:Isoenzymes; D005576:Colforsin; D019319:Okadaic Acid; D015240:Phorbol 12,13-Dibutyrate; C497256:Prkce protein, mouse; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium