背景:能量代谢受损是导致胰岛素抵抗和异位脂肪储存的可能机制。
目的:我们研究了膳食摄入是否对胰岛素敏感和胰岛素抵抗的人的肝磷代谢产物有不同的影响。
方法:Young,精益,胰岛素敏感的人(CONs)[平均±SD体重指数(BMI;kg/m(2)):23.2±1.5];胰岛素抵抗,耐葡萄糖,研究了肥胖者(OBE)(BMI:34.3±1.7)和2型糖尿病患者(T2Ds)(BMI:32.0±2.4)(n=10/组).T2Ds(61±7岁)比OBE(31±7岁)和CONs(28±3岁)年龄大(P<0.001)。我们量化了肝脏γATP,无机磷酸盐(Pi),和脂肪含量[肝细胞脂质(HCL)]在高热量混合餐前和后160和240分钟使用(31)P/(1)H磁共振波谱。在一部分志愿者中,我们使用高分辨率呼吸测量法测量骨骼肌氧化能力.使用高胰岛素-正常血糖钳夹评估全身胰岛素敏感性(M值)。
结果:OBE和T2D具有相似的胰岛素抵抗(M值:3.5±1.4和1.9±2.5mg·kg(-1)·min(-1),分别;P=0.9)和高12倍(P=0.01)和17倍(P=0.002)的HCL,分别,比那些精瘦的人。尽管空腹肝脏γATP浓度相当,OBE中γATP的最大餐后增加量为6倍(0.7±0.2mmol/L;P=0.03),但T2Ds中γATP的最大餐后增加量(0.6±0.2mmol/L;P=0.09)高于CONs(0.1±0.1mmol/L)。然而,在禁食状态下,与CONs相比,T2Ds中的肌肉复合物I活性降低了53%(P=0.01),而OBE中没有(P=0.15)。
结论:Young,肥胖,非糖尿病人类表现出增强的餐后肝脏能量代谢,而老年人T2Ds空腹肌肉能量代谢受损。这些发现支持能量代谢的差异和组织特异性调节的概念,这可以独立于胰岛素抵抗而发生。该试验在clinicaltrials.gov注册为NCT01229059。
BACKGROUND: Impaired energy metabolism is a possible mechanism that contributes to insulin resistance and ectopic fat storage.
OBJECTIVE: We examined whether meal ingestion differently affects hepatic phosphorus metabolites in insulin-sensitive and insulin-resistant humans.
METHODS: Young, lean, insulin-sensitive humans (CONs) [mean ± SD body mass index (BMI; in kg/m(2)): 23.2 ± 1.5]; insulin-resistant, glucose-tolerant, obese humans (OBEs) (BMI: 34.3 ± 1.7); and type 2 diabetes patients (T2Ds) (BMI: 32.0 ± 2.4) were studied (n = 10/group). T2Ds (61 ± 7 y old) were older (P < 0.001) than were OBEs (31 ± 7 y old) and CONs (28 ± 3 y old). We quantified hepatic γATP, inorganic phosphate (Pi), and the fat content [hepatocellular lipids (HCLs)] with the use of (31)P/(1)H magnetic resonance spectroscopy before and at 160 and 240 min after a high-caloric mixed meal. In a subset of volunteers, we measured the skeletal muscle oxidative capacity with the use of high-resolution respirometry. Whole-body insulin sensitivity (M value) was assessed with the use of hyperinsulinemic-euglycemic clamps.
RESULTS: OBEs and T2Ds were similarly insulin resistant (M value: 3.5 ± 1.4 and 1.9 ± 2.5 mg · kg(-1) · min(-1), respectively; P = 0.9) and had 12-fold (P = 0.01) and 17-fold (P = 0.002) higher HCLs, respectively, than those of lean persons. Despite comparable fasting hepatic γATP concentrations, the maximum postprandial increase of γATP was 6-fold higher in OBEs (0.7 ± 0.2 mmol/L; P = 0.03) but only tended to be higher in T2Ds (0.6 ± 0.2 mmol/L; P = 0.09) than in CONs (0.1 ± 0.1 mmol/L). However, in the fasted state, muscle complex I activity was 53% lower (P = 0.01) in T2Ds but not in OBEs (P = 0.15) than in CONs.
CONCLUSIONS: Young, obese, nondiabetic humans exhibit augmented postprandial hepatic energy metabolism, whereas elderly T2Ds have impaired fasting muscle energy metabolism. These findings support the concept of a differential and tissue-specific regulation of energy metabolism, which can occur independently of insulin resistance. This trial was registered at clinicaltrials.gov as NCT01229059.