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• W2043113739 abstract "We hypothesized that altered insulin secretory patterns in obese (fa/fa) Zucker rats might be caused by changes in downstream stimulus–secretion coupling events, such as ATP-dependent potassium (K ATP ) channel activity. The functions of K ATP -dependent and -independent pathways of insulin secretion were therefore compared in lean and fa/fa Zucker rat isolated islets. K ATP channel function was normal in fa/fa rat islets, as assessed by responsiveness to direct channel inactivators glybenclamide and quinine and by the receptor-mediated response to epinephrine and somatostatin. Altered sensitivity to glucose and mannoheptulose were explained by upstream alterations in glucose metabolism documented earlier. Despite normal inactivation of K ATP channels by ATP depletion of fa/fa rat islets, glucose-stimulated insulin secretion was not inhibited, leading to studies of a putative K ATP -independent pathway. When islets were depolarized by incubating with 30 mM potassium and 0.25 mM diazoxide to bypass K ATP channels, glucose elicited a concentration-dependent response in both phenotypes. This response required glucose metabolism and Ca 2+ , as proven by experiments with nonmetabolizable glucose analogs and calcium chelation, but was only partially inhibited by a glycolytic inhibitor. Intermediates or products of oxidative metabolism are likely involved because α-ketoisocaproate also elicited a K ATP -independent insulin response. The pattern of responses was similar in lean and fa/fa rat islets, indicating that neither of these pathways explains the insulin secretion by fa/fa rat islets depleted of ATP. In conclusion, phenotype-related differences in K ATP channel function were consistent with upstream changes in glucose metabolism in fa/fa rat islets. Further studies are required to understand the basis of insulin secretion in ATP-depleted islets from fa/fa rats.Key words: ATP-dependent K channels, insulin secretion, obesity, pancreatic islet, Zucker rat." @default.
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• W2043113739 date "1996-05-01" @default.
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• W2043113739 title "KATP channel-dependent and -independent pathways of insulin secretion in isolated islets from fa/fa Zucker rats" @default.
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• W2043113739 doi "https://doi.org/10.1139/o96-043" @default.
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