Caloric restriction rapidly reverses type 2 diabetes (T2D), but the mechanism(s) of this reversal are poorly understood. Here we show that 3 days of a very-low-calorie diet (VLCD, one-quarter their typical intake) lowered plasma glucose and insulin concentrations in a rat model of T2D without altering body weight. The lower plasma glucose was associated with a 30% reduction in hepatic glucose production resulting from suppression of both gluconeogenesis from pyruvate carboxylase (VPC), explained by a reduction in hepatic acetyl-CoA content, and net hepatic glycogenolysis. In addition, VLCD resulted in reductions in hepatic triglyceride and diacylglycerol content and PKCɛ translocation, associated with improved hepatic insulin sensitivity. Taken together, these data show that there are pleotropic mechanisms by which VLCD reverses hyperglycemia in a rat model of T2D, including reduced DAG-PKCɛ-induced hepatic insulin resistance, reduced hepatic glycogenolysis, and reduced hepatic acetyl-CoA content, PC flux, and gluconeogenesis.

中文翻译：

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低热量饮食在2型糖尿病大鼠模型中逆转高血糖的机制

热量限制会迅速逆转2型糖尿病（T2D），但对这种逆转的机制了解甚少。在这里，我们显示，在T2D大鼠模型中，低热量饮食（VLCD，典型摄入量的四分之一）的三天降低了血浆葡萄糖和胰岛素浓度，而没有改变体重。血浆葡萄糖的降低与丙酮酸羧化酶（VPC）的糖异生作用的抑制引起的肝葡萄糖生成减少30％有关，这可以归因于肝脏乙酰辅酶A含量的减少和净肝糖原分解。此外，VLCD降低了肝甘油三酯和二酰基甘油的含量以及PKCɛ的移位，从而改善了肝对胰岛素的敏感性。在一起