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.
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
W J
WJ
Malaisse
P
P
Lebrun
B
B
Yaylali
J
J
Camara
I
I
Valverde
A
A
Sener
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