Activators of protein kinase C depolarize insulin-secreting cells by closing K+ channels.

摘要: Carbohydrate stimuli of insulin secretion depolarize the pancreatic B cell and B-cell line RINm5F by inhibiting ATP-sensitive K+ channels. We examined possibility that this effect is mediated activation protein kinase C. In cells, triose D-glyceraldehyde evoked a rapid increase mass 1,2-diacylglycerol, endogenous activator This mainly due to de novo synthesis lipid from glycolytic intermediates, as glyceraldehyde carbon was incorporated into 1,2-diacylglycerol within 1 min exposure 14C-labelled glyceraldehyde. The effects two exogenous activators C, 4-beta-12-phorbol-myristate 13-acetate (PMA) 1,2-didecanoylglycerol (DC10) on single channel currents were in cell-attached membrane patches. Both PMA DC10 depolarized cells decreased open-state probability These actions not changes cellular ATP content, since PMA, like glyceraldehyde, failed alter ATP. As case for raised cytosolic free Ca2+ [( Ca2+]i) stimulated secretion. these are inhibited absence external Ca2+. This, attenuation [Ca2+]i rise verapamil, suggest all three raise promoting influx through voltage-gated channels turn leading C mimic it proposed carbohydrate-mediated production constitutes link between metabolism depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)