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Ketone bodies and islet function: sup 45 Ca handling, insulin synthesis, and release

Journal Article · · American Journal of Physiology; (USA)
OSTI ID:6875050

D-(-)-beta-Hydroxybutyrate and acetoacetate cause a rapid, sustained, and rapidly reversible stimulation of insulin release from rat pancreatic islets incubated in the presence, but not absence, of D-glucose. This coincides with stimulation of both proinsulin biosynthesis and {sup 45}Ca net uptake. The ketone bodies also decrease {sup 45}Ca outflow from prelabeled islets perifused in the absence of Ca{sup 2+} and, in contrast, enhance effluent radioactivity in the presence of Ca{sup 2+}. In the presence of D-glucose, the secretory response to D-(-)-beta-hydroxybutyrate is concentration related in the 2.5-20 mM range, abolished in the absence of Ca{sup 2+} or presence of KCN, and enhanced by theophylline and forskolin. It corresponds grossly to a shift to the left of the sigmoidal curve relating insulin output to the ambient concentration of D-glucose. The secretory, biosynthetic, and cationic response to acetoacetate is less marked than that evoked by an equimolar concentration of D-(-)-beta-hydroxybutyrate. These features are compatible with the view that the insulinotropic action of ketone bodies would be causally linked to their metabolism in islet cells.

OSTI ID:
6875050
Journal Information:
American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 259; ISSN 0002-9513; ISSN AJPHA
Country of Publication:
United States
Language:
English