Secretagogue-induced [Ca2+]i changes in single rat pancreatic islets and correlation with simultaneously measured insulin release.
The effects of secretagogues (glucose, tolbutamide and phorbol esters) on simultaneously measured intracellular free calcium concentration ([Ca2+]i) and insulin release were studied in rat pancreatic islets of Langerhans. Stimulatory concentrations (11mM) of glucose caused a transient [Ca2+]i. In contrast with mouse islets, rat islets scarcely showed glucose-induced [Ca2+]i oscillations. Digital image analysis showed that [Ca2+]i changes occurred synchronously across the whole islets. As expected simultaneously measured insulin release was biphasic with a clear second phase. This clearly indicated that in rat islets there is a lack of correlation between [Ca2+]i and insulin release. This was further explored using agents which separately promoted the first (tolbutamide, 200 microns and second (phorbol-12-myristate-13-acetate; PMA; 5nM) phases of insulin release. Tolbutamide induced a transient increase in [Ca2+]i. These results suggest that in rat islets the first phase of insulin release is calcium dependent, whereas the second phase is related to the activation of protein kinase C (PKC). However, the glucose-induced second phase of insulin release did not coincide with an increase in membrane-associated PKC activity. Other messengers may contribute to this late phase of insulin release.
Martin
F
F
Department of Physiology, University of Alicante, Spain.
Reig
J A
JA
Soria
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D005947:Glucose / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology; D007211:Indoles; D007444:Inulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D007930:Leucine / Q000494:pharmacology; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology*
D005456:Fluorescent Dyes; D007211:Indoles; D005973:Glutamine; D002217:Carbachol; D007444:Inulin; D014044:Tolbutamide; D011493:Protein Kinase C; D007930:Leucine; D005947:Glucose; C048960:indo-1; D013755:Tetradecanoylphorbol Acetate; D003981:Diazoxide; D002118:Calcium; D016257:Fura-2