کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2793745 1155183 2006 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes
چکیده انگلیسی

SummaryTo investigate the role of brain insulin action in the pathogenesis and treatment of diabetes, we asked whether neuronal insulin signaling is required for glucose-lowering during insulin treatment of diabetes. Hypothalamic signaling via the insulin receptor substrate-phosphatidylinositol 3-kinase (IRS-PI3K) pathway, a key intracellular mediator of insulin action, was reduced in rats with uncontrolled diabetes induced by streptozotocin (STZ-DM). Further, infusion of a PI3K inhibitor into the third cerebral ventricle of STZ-DM rats prior to peripheral insulin injection attenuated insulin-induced glucose lowering by ∼35%–40% in both acute and chronic insulin treatment paradigms. Conversely, increased PI3K signaling induced by hypothalamic overexpression of either IRS-2 or protein kinase B (PKB, a key downstream mediator of PI3K action) enhanced the glycemic response to insulin by ∼2-fold in STZ-DM rats. We conclude that hypothalamic insulin signaling via the IRS-PI3K pathway is a key determinant of the response to insulin in the management of uncontrolled diabetes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 3, Issue 1, January 2006, Pages 67–73
نویسندگان
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