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- W2165225267 abstract "We have studied the involvement of central nervous system (CNS) insulin receptors in mediating the central hypoglycemic effect of insulin by using insulin derivatives modified at regions of the hormone necessary for receptor reactivity and peripheral bioactivity. Acetylation or succinylation of the 3 free amino groups of insulin at positions A1, B1 and B29 resulted in a corresponding decrease in lipogenic activity in isolated rat adipocytes, with concentrations of hormone required to produce half the maximal effect (ED50) being 0.15 ng/ml, 3 ng/ml and 50 ng/ml for native insulin, acetyl3 insulin and succinyl3 insulin, respectively. Moreover, the modified insulins exhibited diminished hypoglycemic effect following central administration in mice, with the doses needed for suppresion of plasma glucose to 50% of basal levels being 1 μg, 10 μg and 25 μg for native insulin, acetyl3 insulin and succinyl3 insulin, respectively. Because binding of insulin derivatives to CNS receptors can be predicted from their peripheral bioactivity, the present finding of parallel decrements in lipogenic activity in vitro and central hypoglycemic effect in vivo, following modification of insulin at regions implicated in receptor activation, is consistent with the view that insulin exerts its central effect on plasma glucose by interacting with specific CNS receptor sites which are closely related to the peripheral insulin receptors." @default.
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- W2165225267 date "1987-08-01" @default.
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- W2165225267 title "Centrally mediated hypoglycemic effect of insulin: apparent involvement of specific insulin receptors" @default.
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- W2165225267 doi "https://doi.org/10.1016/0006-8993(87)90972-3" @default.
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