Fueger Patrick T, Bracy Deanna P, Malabanan Carlo M, Pencek R Richard, Granner Daryl K, Wasserman David H
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Diabetes. 2004 Feb;53(2):306-14. doi: 10.2337/diabetes.53.2.306.
The aim of the present study was to determine the specific sites of impairment to muscle glucose uptake (MGU) in the insulin-resistant high-fat-fed, conscious C57BL/6J mouse. Wild type (WT) and hexokinase II overexpressing (HK(Tg)) mice were fed either a standard diet or high-fat diet and studied at 4 months of age. A carotid artery and jugular veins had catheters chronically implanted for sampling and infusions, respectively, and mice were allowed to recovery for at least 5 days. Mice were fasted for 5 h and underwent a hyperinsulinemic-euglycemic clamp or saline infusion for 120 min. Separate groups of mice were studied during 30-min sedentary or treadmill exercise periods. A bolus of 2-deoxy[(3)H]glucose was administered 25 min before the end of each study for determination of R(g), an index of tissue-specific glucose uptake. Fasting blood glucose was increased in high-fat compared with standard diet-fed WT (194 +/- 4 vs. 171 +/- 4 mg/dl) but not HK(Tg) (179 +/- 5 vs. 171 +/- 3 mg/dl) mice. High-fat feeding created hyperinsulinemia in both WT and HK(Tg) mice (58 +/- 8 and 77 +/- 15 micro U/ml) compared with standard diet-fed mice (21 +/- 2 and 20 +/- 1 micro U/ml). R(g) was not affected by genotype or diet during either saline infusion or sedentary conditions. HK II overexpression augmented insulin-stimulated R(g) in standard diet-fed but not high-fat-fed mice. Exercise-stimulated R(g) was impaired by high-fat feeding in WT mice, but this impairment was largely rectified in HK(Tg) mice. In conclusion, high-fat feeding impairs both insulin- and exercise-stimulated MGU, but only exercise-stimulated MGU was corrected by HK II overexpression.
本研究的目的是确定胰岛素抵抗的高脂喂养清醒C57BL/6J小鼠肌肉葡萄糖摄取（MGU）受损的具体部位。野生型（WT）和己糖激酶II过表达（HK(Tg)）小鼠分别喂食标准饮食或高脂饮食，并在4月龄时进行研究。分别长期植入颈动脉导管和颈静脉导管用于采样和输注，小鼠恢复至少5天。小鼠禁食5小时，然后进行高胰岛素-正常血糖钳夹或生理盐水输注120分钟。在30分钟的久坐或跑步机运动期间对不同组的小鼠进行研究。在每项研究结束前25分钟给予一剂2-脱氧[(3)H]葡萄糖以测定R(g)，这是组织特异性葡萄糖摄取的指标。与标准饮食喂养的WT小鼠（194±4 vs. 171±4 mg/dl）相比，高脂喂养使空腹血糖升高，但HK(Tg)小鼠（179±5 vs. 171±3 mg/dl）未出现这种情况。与标准饮食喂养的小鼠（21±2和20±1 μU/ml）相比，高脂喂养使WT和HK(Tg)小鼠均出现高胰岛素血症（58±8和77±15 μU/ml）。在生理盐水输注或久坐条件下，R(g)不受基因型或饮食的影响。HK II过表达增强了标准饮食喂养而非高脂喂养小鼠中胰岛素刺激的R(g)。高脂喂养损害了WT小鼠运动刺激的R(g)，但在HK(Tg)小鼠中这种损害基本得到纠正。总之，高脂喂养损害了胰岛素和运动刺激的MGU，但只有运动刺激的MGU通过HK II过表达得到纠正。
