ATP-SENSITIVE K-INDEPENDENT GLUCOSE ACTION IN RAT PANCREATIC BETA-CELL( CHANNEL)

The nature of ATP-sensitive K+ (K-ATP(+)) channel-independent, insulin otropic action of glucose was investigated using nonglucose-primed pan creatic islets. When the beta-cell was depolarized with K+, glucose do se dependently stimulated insulin release despite inhibition of the K- ATP(+), channel closure by diazoxide. K+ depolarization could be repla ced with BAY K 8644, a calcium channel agonist. Prior fasting of rats and lowering ambient temperature greatly suppressed glucose oxidation and utilization by the islet cells and abolished insulin release in re sponse to high glucose alone. However, under these conditions, the K-A TP(+), channel-independent, glucose-induced insulin release was clearl y demonstrable. p-Nitrophenyl-alpha-D-glucopyranoside (sweet taste inh ibitor) but not its beta-isomer, neomycin (phospholipase C inhibitor) and staurosporine (C kinase blocker) inhibited the K-ATP(+) channel-in dependent, insulinotropic action of glucose. For the K-ATP(+), channel -independent glucose-induced insulin release 1) elevation of cytosolic calcium is required, 2) minute glucose metabolism is enough, if gluco se metabolism is necessary, and 3) direct recognition of glucose molec ule, phospholipase C, and protein kinase C appear to be involved.