Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes

被引:91
作者
Perry, Rachel J. [1 ]
Peng, Liang [1 ,2 ]
Cline, Gary W. [1 ]
Wang, Yongliang [1 ]
Rabin-Court, Aviva [1 ]
Song, Joongyu D. [1 ]
Zhang, Dongyan [4 ]
Zhang, Xian-Man [1 ]
Nozaki, Yuichi [1 ]
Dufour, Sylvie [4 ]
Petersen, Kitt Falk [1 ]
Shulman, Gerald I. [1 ,3 ,4 ]
机构
[1] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA
[2] China Japan Friendship Hosp, Inst Clin Med Sci, Beijing 100029, Peoples R China
[3] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA
[4] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA
关键词
HEPATIC INSULIN-RESISTANCE; Y GASTRIC BYPASS; BETA-CELL FUNCTION; FATTY LIVER-DISEASE; BARIATRIC SURGERY; HYPOCALORIC DIET; WEIGHT-LOSS; MELLITUS; GLUCOSE; METAANALYSIS;
D O I
10.1016/j.cmet.2017.10.004
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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 PKC epsilon 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-PKC epsilon-induced hepatic insulin resistance, reduced hepatic glycogenolysis, and reduced hepatic acetyl-CoA content, PC flux, and gluconeogenesis.
引用
收藏
页码:210 / +
页数:11
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