Ketone bodies and islet function: 45Ca handling, insulin synthesis, and release.
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 45Ca net uptake. The ketone bodies also decrease 45Ca outflow from prelabeled islets perifused in the absence of Ca2+ and, in contrast, enhance effluent radioactivity in the presence of Ca2+. 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 Ca2+ 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.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Lebrun
P
P
Yaylali
B
B
Camara
J
J
Valverde
I
I
Sener
A
A
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D005947:Glucose / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000096:biosynthesis* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007657:Ketone Bodies / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010477:Perfusion; D010649:Phenylalanine / Q000378:metabolism; D011384:Proinsulin / Q000096:biosynthesis; D051381:Rats
D000090:Acetoacetates; D002132:Calcium Radioisotopes; D006885:Hydroxybutyrates; D007328:Insulin; D007657:Ketone Bodies; D010649:Phenylalanine; C016635:acetoacetic acid; D011384:Proinsulin; D005947:Glucose; D002118:Calcium; D020155:3-Hydroxybutyric Acid