Johnson Matthew L, Distelmaier Klaus, Lanza Ian R, Irving Brian A, Robinson Matthew M, Konopka Adam R, Shulman Gerald I, Nair K Sreekumaran
Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN.
Howard Hughes Medical Institute and the Departments of Medicine and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT.
Diabetes. 2016 Jan;65(1):74-84. doi: 10.2337/db15-0675. Epub 2015 Aug 31.
Caloric restriction (CR) improves insulin sensitivity and reduces the incidence of diabetes in obese individuals. The underlying mechanisms whereby CR improves insulin sensitivity are not clear. We evaluated the effect of 16 weeks of CR on whole-body insulin sensitivity by pancreatic clamp before and after CR in 11 obese participants (BMI = 35 kg/m(2)) compared with 9 matched control subjects (BMI = 34 kg/m(2)). Compared with the control subjects, CR increased the glucose infusion rate needed to maintain euglycemia during hyperinsulinemia, indicating enhancement of peripheral insulin sensitivity. This improvement in insulin sensitivity was not accompanied by changes in skeletal muscle mitochondrial oxidative capacity or oxidant emissions, nor were there changes in skeletal muscle ceramide, diacylglycerol, or amino acid metabolite levels. However, CR lowered insulin-stimulated thioredoxin-interacting protein (TXNIP) levels and enhanced nonoxidative glucose disposal. These results support a role for TXNIP in mediating the improvement in peripheral insulin sensitivity after CR.
热量限制（CR）可提高肥胖个体的胰岛素敏感性，并降低糖尿病的发病率。CR改善胰岛素敏感性的潜在机制尚不清楚。我们评估了11名肥胖参与者（BMI = 35 kg/m²）在CR前后通过胰腺钳夹法进行的16周CR对全身胰岛素敏感性的影响，并与9名匹配的对照受试者（BMI = 34 kg/m²）进行比较。与对照受试者相比，CR增加了在高胰岛素血症期间维持血糖正常所需的葡萄糖输注速率，表明外周胰岛素敏感性增强。胰岛素敏感性的这种改善并未伴随骨骼肌线粒体氧化能力或氧化剂释放的变化，骨骼肌神经酰胺、二酰甘油或氨基酸代谢物水平也没有变化。然而，CR降低了胰岛素刺激的硫氧还蛋白相互作用蛋白（TXNIP）水平，并增强了非氧化葡萄糖处置。这些结果支持TXNIP在介导CR后外周胰岛素敏感性改善中发挥作用。
