Steno Diabetes Centre, Gentofte, Denmark.
Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E555-64. doi: 10.1152/ajpendo.00223.2009. Epub 2009 Dec 8.
Individuals born with low birth weight (LBW) are at risk of developing type 2 diabetes mellitus (T2D), which may be precipitated by physical inactivity. Twenty-two LBW subjects and twenty-three controls were studied before and after bed rest by the hyperinsulinemic euglycemic clamp combined with indirect calorimetry and infusion of stable isotope tracers and preceded by an intravenous glucose tolerance test. LBW subjects had a similar body mass index but elevated abdominal obesity compared with controls. The basal rate of whole body lipolysis (WBL) was elevated in LBW subjects with and without correction for abdominal obesity before and after bed rest (all P = 0.01). Skeletal muscle hormone-sensitive lipase (HSL) protein expression and phosphorylation at Ser565 were similar in the two groups. Bed rest resulted in a decrease in WBL and an increased skeletal muscle HSL Ser565 phosphorylation indicating a decreased HSL activity in both groups. All subjects developed peripheral insulin resistance in response to bed rest (all P < 0.0001) with no differences between groups. LBW subjects developed hepatic insulin resistance in response to bed rest. In conclusion, increased WBL may contribute to the development of hepatic insulin resistance when exposed to bed rest in LBW subjects. Nine days of bed rest causes severe peripheral insulin resistance and reduced WBL and skeletal muscle HSL activity, as well as a compensatory increased insulin secretion, with no differences in LBW subjects and controls.
出生体重低(LBW)的个体有患 2 型糖尿病(T2D)的风险,这种风险可能因缺乏体力活动而加剧。在卧床休息前后,通过高胰岛素正常血糖钳夹联合间接热量测定和稳定同位素示踪剂输注,对 22 名 LBW 受试者和 23 名对照者进行了研究,在此之前还进行了静脉葡萄糖耐量试验。LBW 受试者的体重指数与对照组相似,但腹部肥胖程度更高。LBW 受试者在卧床休息前后(所有 P=0.01),无论是否校正腹部肥胖,全身脂肪分解率(WBL)的基础速率均升高。两组的骨骼肌激素敏感性脂肪酶(HSL)蛋白表达和 Ser565 磷酸化相似。卧床休息导致 WBL 减少和骨骼肌 HSL Ser565 磷酸化增加,表明两组的 HSL 活性均降低。所有受试者在卧床休息时均出现外周胰岛素抵抗(所有 P<0.0001),两组之间无差异。LBW 受试者在卧床休息时出现肝胰岛素抵抗。总之,在 LBW 受试者中,卧床休息时增加的 WBL 可能导致肝胰岛素抵抗的发展。9 天的卧床休息导致严重的外周胰岛素抵抗和 WBL 及骨骼肌 HSL 活性降低,以及代偿性胰岛素分泌增加,LBW 受试者和对照组之间无差异。