Parathyroid hormone activates protein kinase C of pancreatic islets.
Pancreatic islets are targets for PTH. The acute exposure of the islets to PTH results in a rise in their cytosolic calcium ([Ca2+]i). It also stimulates insulin secretion in a manner similar to that produced by phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C (PKC), suggesting that the hormone may stimulate the activity of this enzyme. The present study examined the effect of PTH (1-34) on both cytosolic and membrane bound PKC activity of pancreatic islets and compared it with that of glucose and TPA. In the basal state, PKC activity is predominantly found in the cytosol. Both PTH or high glucose concentration caused a significant increase in membrane-bound and total PKC activity, whereas cytosolic enzyme activity remained unchanged. The effects of these two agonists peaked at 5 min and declined thereafter. The effect of PTH on PKC activity was abolished by the PTH antagonist ([Tyr-34] bovine PTH (7-34) NH2). In contrast, TPA induced a rise in membrane-bound PKC activity with simultaneous decrease in cytosolic pool of PKC without a change in total PKC activity. Removal of calcium from the incubation media resulted in partial and significant loss of PTH-induced rise in membrane-bound PKC activity. The data demonstrated that 1) PTH stimulate PKC activity of pancreatic islets in a manner similar to that of glucose, 2) both of the agonists increases total PKC activity of islets and translocation of the enzyme activity to the membranes of the islets, and 3) the effect of PTH is mediated, in part, by its ability to augment calcium entry into the islets and is most likely receptor mediated.
Sahai
A
A
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Fadda
G Z
GZ
Massry
S G
SG
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003470:Culture Media; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003470:Culture Media; D010281:Parathyroid Hormone; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium