Ketone bodies and islet function: 86Rb handling and metabolic data.
The metabolism of ketone bodies was investigated in rat pancreatic islets incubated in the absence or presence of D-glucose. The generation of 14CO2 from 3-14C-labeled ketone bodies, the interconversion of D-(-)-beta-hydroxybutyrate and acetoacetate (AcAc), the reciprocal effects of ketone bodies and D-glucose on their respective catabolism, and the influence of these exogenous nutrients on the output of 14CO2 from islets preincubated with either L-[U-14C]glutamine or [U-14C]palmitate provided an estimation of the nutrient-induced changes in O2 uptake that was in fair agreement with the observed modifications of islet respiration. There was a close correlation between such changes and the corresponding values for insulin output. Because the stimulation of insulin release by ketone bodies also coincided with a decrease in 86Rb outflow from prelabeled islets, these findings suggest that the insulinotropic action of ketone bodies is causally linked to their catabolism through an increase in ATP generation rate and a subsequent decrease in K+ conductance. A complementary participation of changes in mitochondrial redox state to stimulus-secretion coupling is considered, however, in the light of comparisons between the effects of D-(-)-beta-hydroxybutyrate and AcAc, respectively, on mitochondrial NADH generation, 45Ca net uptake, and D-[6-14C]glucose oxidation.
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
W J
WJ
Malaisse
P
P
Lebrun
J
J
Rasschaert
F
F
Blachier
T
T
Yilmaz
A
A
Sener
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D006884:Hydroxybutyrate Dehydrogenase / Q000378:metabolism; D006885:Hydroxybutyrates / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007657:Ketone Bodies / Q000494:pharmacology*; D007700:Kinetics; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000378:metabolism*; D012414:Rubidium Radioisotopes
D000090:Acetoacetates; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D012414:Rubidium Radioisotopes; C016635:acetoacetic acid; D006884:Hydroxybutyrate Dehydrogenase; D005947:Glucose; D012413:Rubidium; D020155:3-Hydroxybutyric Acid