Dear Editor, Gluconeogenesis is one of the major mechanisms to main- tain hepatic glucose homeostasis and dysregulation of hepatic gluconeogenesis contributes to hyperglycemia in type 2 diabetes. Under fasted conditio...Dear Editor, Gluconeogenesis is one of the major mechanisms to main- tain hepatic glucose homeostasis and dysregulation of hepatic gluconeogenesis contributes to hyperglycemia in type 2 diabetes. Under fasted conditions, increases in cir- culating glucagon promote hepatic glucose production through activation of gluconeogenic pathway by HDAC5 and CREB coactivator CRTC2 （Lv et al., 2016; Lv et al., 2017; Qiu et al., 2017）. The circadian clock coordinates behavior and metabolism into rhythms not only in the central hypothalamus but also in peripheral tissues （Marcheva et al., 2010; Vollmers et al., 2009）. Transcription factor BMAL1 heterodimerizes with CLOCK to activate the expression of Per and Cry, which in turn suppress CLOCK/BMAL1 activity （Reppert ＆ Weaver, 2002）. Although BMAL1 knockout mice show fasting hypoglycemia （Rudic et al., 2004）, the detailed mechanism of BMAL1 regulation on hepatic gluco- neogenesis has not been thoroughly understood.展开更多
文摘Dear Editor, Gluconeogenesis is one of the major mechanisms to main- tain hepatic glucose homeostasis and dysregulation of hepatic gluconeogenesis contributes to hyperglycemia in type 2 diabetes. Under fasted conditions, increases in cir- culating glucagon promote hepatic glucose production through activation of gluconeogenic pathway by HDAC5 and CREB coactivator CRTC2 （Lv et al., 2016; Lv et al., 2017; Qiu et al., 2017）. The circadian clock coordinates behavior and metabolism into rhythms not only in the central hypothalamus but also in peripheral tissues （Marcheva et al., 2010; Vollmers et al., 2009）. Transcription factor BMAL1 heterodimerizes with CLOCK to activate the expression of Per and Cry, which in turn suppress CLOCK/BMAL1 activity （Reppert ＆ Weaver, 2002）. Although BMAL1 knockout mice show fasting hypoglycemia （Rudic et al., 2004）, the detailed mechanism of BMAL1 regulation on hepatic gluco- neogenesis has not been thoroughly understood.
