Abstract
The mechanisms by which arginine-vasopressin (AVP) affects pancreatic B-cell function were studied in normal mouse islets. AVP produced a dose-dependent (0.1-1000 nM; EC50 approximately 1-2 nM) amplification of glucose-induced insulin release. This amplification was of slow onset and reversibility. AVP was ineffective when the concentration of glucose was less than 7 mM, but was still very effective in 30 mM glucose. The increase in insulin release produced by AVP was accompanied by small accelerations of 86Rb and 45Ca efflux from islet cells. Omission of extracellular Ca2+ accentuated the effect of AVP on 86Rb efflux, attenuated that on 45Ca efflux, and abolished that on release. Under no condition did AVP inhibit 86Rb efflux. AVP did not significantly affect cAMP levels, but increased inositol phosphate levels in islet cells, even in the absence of extracellular Ca2+. AVP did not affect the membrane potential in unstimulated B-cells and augmented glucose-induced electrical activity only slightly. This was not due to a direct action on ATP-sensitive K+ channels as revealed by patch-clamp recordings (whole cell and outside-out patches). In conclusion, AVP is not an initiator of insulin release, but it potently amplifies glucose-induced insulin release in normal mouse B-cells. This effect involves a stimulation of phosphoinositide metabolism, and presumably an activation of protein kinase C, rather than a change in cAMP levels or a direct control of the membrane potential.
Highlights
The mechanisms by which arginine-vasopressin (AVP) affects pancreatic B-cell function were studied in normal mouse islets
The increase in insulin release produced by AVP was accompanied by small accelerations of “Rb and 46Ca efflux from islet cells
Evidence will be presented that AVP potently amplifies glucose-induced insulin release by mechanisms that involve stimulation of phosphoinositide metabolism rather than changes in CAMP levels or in B-cell membrane potential
Summary
It is well established that AVP exerts glycogenolytic and gluconeogenic actions on the liver [1, 2] These effects are, at least partly, due to a receptor-mediated hydrolysis of membrane phosphatidylinositol4&bisphosphate with subsequent mobilization of intracellular Ca2+ by inositol 1,4,5trisphosphate, and activation of protein kinase C by diacylglycerol [3, 4]. An increase in CAMP levels was observed in rat islets stimulated by AVP [13] This could be suggestive of the existence of a V2-type receptor [16], but cannot explain the inhibition of insulin release that was concomitantly observed. Two additional effects of AVP in RINm5F cells have been reported very recently [17] It mobilized intracellular Ca*+ and depolarized the plasma membrane by closing ATP-sensitive K’ channels. Evidence will be presented that AVP potently amplifies glucose-induced insulin release by mechanisms that involve stimulation of phosphoinositide metabolism rather than changes in CAMP levels or in B-cell membrane potential
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
