Pdx1 restores β cell function in Irs2 knockout mice

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Pdx1 restores β cell function in Irs2 knockout mice

The insulin receptor substrates (IRS proteins) coordinate many signals during insulin and IGF-1 stimulation, including activation of the phosphatidylinositol (PI) 3-kinase and ERK1/2 cascades (1). Although highly homologous and universally expressed, Irs1 and Irs2 display distinct biological function in mice (2). Irs1 strongly promotes somatic growth and mediates insulin action upon carbohydrat...

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Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice.

The capacity of pancreatic β cells to maintain glucose homeostasis during chronic physiologic and immunologic stress is important for cellular and metabolic homeostasis. Insulin receptor substrate 2 (IRS2) is a regulated adapter protein that links the insulin and IGF1 receptors to downstream signaling cascades. Since strategies to maintain or increase IRS2 expression can promote β cell growth, ...

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Pancreatic β Cell Mass Preserved in Heterozygous PDK1 Knockout Mice

We have demonstrated that 3-phosphoinositide-dependent protein kinase 1 (PDK1) contributes to signaling by insulin or insulin-like growth fctor-1 (IGF-1) that is responsible for the regulation of both the number and size of pancreatic β cells in mice. Complete ablation of PDK1 in pancreatic β cells leads to progressive hyperglycemia as a result of loss of β cell mass. In this study, we generate...

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Chemerin regulates β-cell function in mice

Although various function of chemerin have been suggested, its physiological role remains to be elucidated. Here we show that chemerin-deficient mice are glucose intolerant irrespective of exhibiting reduced macrophage accumulation in adipose tissue. The glucose intolerance was mainly due to increased hepatic glucose production and impaired insulin secretion. Chemerin and its receptor ChemR23 w...

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Loss of Nix in Pdx1-deficient mice prevents apoptotic and necrotic β cell death and diabetes.

Mutations in pancreatic duodenal homeobox (PDX1) are linked to human type 2 diabetes and maturity-onset diabetes of the young type 4. Consistent with this, Pdx1-haploinsufficient mice develop diabetes. Both apoptosis and necrosis of β cells are mechanistically implicated in diabetes in these mice, but a molecular link between Pdx1 and these 2 forms of cell death has not been defined. In this st...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2002

ISSN: 0021-9738

DOI: 10.1172/jci200214439