PHOSPHATE FLUSH AND GLUCOSE-METABOLISM IN PANCREATIC-ISLETS OF YOUNG AND OLD DIABETIC MICE (C57BL/KSJ-DB/DB)

Pancreatic islets from normal C57BL/KsJ-+/+-mice and diabetic C57BL/KsJ-db/db-mice were collagenase-isolated and incubated with 33P-labeled inorganic phosphate. No significant difference was observed in phosphate uptake between normal and diabetic mouse islets whether the animals were young (6-8 wk) or old (27 .+-. 9 wk). When 33P-labeled islets were perifused with non-radioactive medium, all types of islets exhibited a brisk and transient peak of phosphate release in response to a change of glucose concentration from 2.8 to 16.7 mmol/l. Expressed in absolute terms, both the basal and peak efflux of phosphate appeared to be diminished in the diabetic mice. In relative terms (peak over basal), the glucose-stimulated phosphate efflux was not lower in diabetic than in normal mice. At both a low (3 mmol/l) and a high (20 mmol/l) glucose concentration, the production of 3H2O from D-[5-3H]glucose was reduced in old but not in young diabetic mouse islets. The percentage increase in glucose metabolism in response to a rise in glucose concentration from 3 to 20 mmol/l was about the same in all types of islets. Disturbed ionic fluxes in the pancreatic islets of diabetic KsJ-db/db-mice are implicated. These effects are probably not due to gross alterations in glycolytic metabolism but more probably reflect alterations in the function of the .beta.-cell plasma membrane.