单位：[1]Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA[2]Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China[3]Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA[4]Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
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.
基金：
United States Public Health ServiceUnited States Department of Health & Human ServicesUnited States Public Health Service [R01 DK40936, P30 DK059635, R01 AG23686, T32 DK101019, K99 CA215315, R01 DK113984 R01 NS087568]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [K99CA215315] Funding Source: NIH RePORTER; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [UL1TR001863] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01DK040936, P30DK045735, R01DK113984, T32DK101019, U24DK059635] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01NS087568] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGINGUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01AG023686] Funding Source: NIH RePORTER
第一作者单位：[1]Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
通讯作者：
通讯机构：[1]Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA[3]Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA[4]Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
推荐引用方式(GB/T 7714)：
Perry Rachel J.,Peng Liang,Cline Gary W.,et al.Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes[J].CELL METABOLISM.2018,27(1):210-+.doi:10.1016/j.cmet.2017.10.004.
APA：
Perry, Rachel J.,Peng, Liang,Cline, Gary W.,Wang, Yongliang,Rabin-Court, Aviva...&Shulman, Gerald I..(2018).Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes.CELL METABOLISM,27,(1)
MLA：
Perry, Rachel J.,et al."Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes".CELL METABOLISM 27..1(2018):210-+
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