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 (V_PC), 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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极低热量饮食在 2 型糖尿病大鼠模型中逆转高血糖的机制。

热量限制可迅速逆转 2 型糖尿病 (T2D)，但人们对这种逆转的机制知之甚少。在这里，我们展示了 3 天的极低热量饮食（VLCD，其典型摄入量的四分之一）降低了 T2D 大鼠模型中的血浆葡萄糖和胰岛素浓度，而不会改变体重。较低的血浆葡萄糖与肝脏葡萄糖生成减少 30% 相关，这是由于丙酮酸羧化酶 (V _PC)，通过减少肝乙酰辅酶A含量和净肝糖原分解来解释。此外，VLCD 导致肝脏甘油三酯和甘油二酯含量降低以及 PKCɛ 易位，这与肝脏胰岛素敏感性的改善有关。总之，这些数据表明，VLCD 可通过多种机制逆转 T2D 大鼠模型中的高血糖，包括减少 DAG-PKCɛ 诱导的肝脏胰岛素抵抗、减少肝糖原分解和减少肝乙酰辅酶 A 含量、PC 通量和糖异生。