A microchemical technic was applied to elucidate the possible role of ATP in insulin secretion by measuring the levels of this metabolite in pancreatic islets from obese hyperglycemic mice. The β cell content of ATP was markedly reduced within the first minute after interruption of the blood supply. A steady-state level of about 5 mmoles of ATP was noted in islets incubated in the absence of glucose. The corresponding ATP level was twice as high when at least 1 mg./ml. of glucose was present in the incubation medium. While the contents of ATP and glycogen remained constant when the pancreatic islets were incubated with diazoxide, the amounts of both these metabolites were significantly reduced by concentrations of sulfonylurea compounds known to stimulate the insulin release. The sulfonylurea effect on the islet ATP content implies a change in the “phosphate potential” of the β cells, which might stimulate glycogenolysis and increase the glycolytic flux. The sulfonylurea stimulation of insulin release might thus be related to a product of glucose degradation beyond the level of glucose-6-phosphate.

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