Glucose-induced activation of pyruvate dehydrogenase in isolated rat pancreatic islets.
1. Rat pancreatic islets were isolated and then maintained in culture for 2-4 days before being incubated in groups of 100 in the presence of different glucose (0-20 mM) or CaCl2 (1.2-4.2 mM) concentrations, or with uncoupler. 2. Increases in extracellular glucose concentration resulted in increases in the amount of active, non-phosphorylated, pyruvate dehydrogenase in the islets, with half-maximal effects around 5-6 mM-glucose. Increasing extracellular glucose from 3 to 20 mM resulted in a 4-6-fold activation of pyruvate dehydrogenase within 2 min. 3. The total enzyme activity was unchanged, and averaged 0.4 m-unit/100 islets at 37 degrees C. 4. These changes in active pyruvate dehydrogenase were broadly similar to changes in insulin secretion by the islets. 5. Increasing extracellular Ca2+ or adding uncoupler also activated pyruvate dehydrogenase to a similar degree, but only the former was associated with increased insulin secretion.
Department of Biochemistry, University of Leeds, U.K.
J G
JG
McCormack
E A
EA
Longo
B E
BE
Corkey
D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats
D011768:Pyruvate Dehydrogenase Complex; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D005947:Glucose; D002122:Calcium Chloride