Regulation of distinct pools of protein kinase C delta in beta cells.
Previous studies from our laboratory have demonstrated the presence of several isoforms of protein kinase C (PKC), Ca(2+)-independent and Ca(2+)-dependent, in both whole islets and tumor-derived beta cells. In the basal state, a major proportion of the isoform was found in the crude membrane fraction with smaller amounts found in both the cytosolic and cytoskeletal fractions. Whole islets showed a similar distribution of the isoform. These studies were done to analyze the effects of insulin secretagogues on the distribution of PKC delta to different cellular pools in isolated insulinoma beta cells. The phorbol ester, phorbol 12-myristate 13-acetate (PMA), produced a transient association of PKC delta with the beta cell cytoskeleton along with sustained decreases in cytosolic enzyme and transient increases in membrane enzyme. Neither glucose nor carbachol could acutely affect the subcellular distribution of PKC delta. Oleic acid decreased the amount of the enzyme associated with the cytoskeleton and led to a sustained decrease of cytosolic enzyme and a transient increase in membrane enzyme. Oleic acid was also able to prevent the increase in cytoskeletal enzyme induced by PMA. Both oleic acid and PMA potentiated glucose-induced insulin release but oleic acid, in contrast to PMA, was unable to initiate insulin release in the presence of substimulatory concentrations of glucose. These data demonstrate that different activators of PKC may have different effects on localization of the enzyme within the cells and suggest that there are at least three apparently distinct pools of PKC delta within the beta cell which may be important in insulin secretion or other aspects of beta cell function.
Knutson
K L
KL
Department of Physiology and Pharmacology, University of Georgia, Athens 30602, USA.
Hoenig
M
M
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007340:Insulinoma / Q000201:enzymology; D007515:Islets of Langerhans / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D019301:Oleic Acid / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007328:Insulin; D007527:Isoenzymes; D019301:Oleic Acid; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate