Control of Glucose Homeostatis through Ubiquitin-Specific Protease 2.

[摘要] Hepatic gluconeogenesis is important for maintaining steady blood glucose levels during starvation and through light/dark cycles. The regulatory network that transduces hormonal and circadian signals serves to integrate these physiological cues and adjust glucose synthesis and secretion by the liver. In this study, we identified ubiquitin-specific protease 2 (USP2) as an inducible regulator of hepatic gluconeogenesis that responds to nutritional status and clock. Adenoviral-mediated expression of USP2 in the liver promotes hepatic glucose production, whereas RNAi knockdown of this factor results in hypoglycemia due to impaired hepatic gluconeogenesis. USP2 is required for maintaining diurnal glucose homeostasis during restricted feeding. Elevated hepatic gluconeogenesis exacerbates the development of hyperglycemia in diabetes. In vivo gain- and loss-of-function studies indicate that USP2 regulates systemic glucose metabolism in insulin resistant state through modulation of hepatic glucocorticoid signaling and the gluconeogenic program. Together, these studies delineate a novel pathway that links hormonal and clock signaling to hepatic gluconeogenesis and glucose homeostasis.

[发布机构] University of Michigan

[效力级别] Gluconeogenesis

[关键词] Glucose Homeostasis;Gluconeogenesis;Glucocorticoids;Molecular;Cellular and Developmental Biology;Science;Cellular & Molecular Biology