Pender C, Goldfine I D, Tanner C J, Pories W J, MacDonald K G, Havel P J, Houmard J A, Youngren J F
Department of Medicine, Division of Diabetes and Endocrine Research, Mount Zion Medical Center, University of California, San Francisco, San Francisco, CA, USA.
Int J Obes Relat Metab Disord. 2004 Mar;28(3):363-9. doi: 10.1038/sj.ijo.0802565.
Obesity results in insulin resistance. Bariatric surgery for obese individuals induces weight loss, improves insulin sensitivity, and lowers insulin levels. We investigated the mechanisms of this improvement.
Insulin receptor (IR) content, IR signaling, and adiponectin levels were measured in nine morbidly obese subjects before and after bariatric surgery.
Seven female and two male, average age 44+/-2y, BMI >40 kg/m(2) and/or at least 100 lbs over ideal body weight, undergoing elective bariatric surgery.
Before surgery BMI, fasting plasma glucose, adiponectin, and insulin levels were measured. A fasting muscle biopsy was obtained from the vastus lateralis for IR concentration and autophosphorylation activity measurements. These procedures were repeated 1 y after surgery.
At 1 y after surgery, the subjects had lost an average of 48.3+/-5.6 kg (P<0.001), insulin sensitivity had significantly increased as determined by the minimal model (SI 0.72+/-0.18 vs 3.86+/-1.43, P<0.05), and IR content had increased two-fold in muscle (2.1+/-0.4 vs 4.3+/-0.7 ng/mg protein, P<0.01). The increase in IR content was related to fasting insulin levels. In the subjects with the lowest IR function, there was also an increase in IR function. Plasma adiponectin increased by 40% following weight loss (7.4+/-1.6 pre vs 10.3+/-1.3 mg/ml post, P<0.05). There was no significant change in muscle content of the IR inhibitor, PC-1.
Increased IR content, most likely regulated by insulin levels, may be one contributor to the increased insulin sensitivity that occurs when morbidly obese patients undergo bariatric surgery.
肥胖会导致胰岛素抵抗。针对肥胖个体进行的减肥手术可引起体重减轻、改善胰岛素敏感性并降低胰岛素水平。我们研究了这种改善的机制。
在9名病态肥胖受试者接受减肥手术前后，测量胰岛素受体（IR）含量、IR信号传导及脂联素水平。
7名女性和2名男性，平均年龄44±2岁，体重指数（BMI）>40 kg/m²且/或比理想体重至少超重100磅，接受择期减肥手术。
术前测量BMI、空腹血糖、脂联素和胰岛素水平。从股外侧肌获取空腹肌肉活检样本，用于测量IR浓度和自磷酸化活性。术后1年重复这些操作。
术后1年，受试者平均体重减轻48.3±5.6 kg（P<0.001），根据最小模型测定，胰岛素敏感性显著增加（胰岛素敏感指数[SI]：术前0.72±0.18，术后3.86±1.43，P<0.05），肌肉中IR含量增加了两倍（术前2.1±0.4 ng/mg蛋白质，术后4.3±0.7 ng/mg蛋白质，P<0.01）。IR含量的增加与空腹胰岛素水平相关。在IR功能最低的受试者中，IR功能也有所增加。体重减轻后血浆脂联素增加了40%（术前7.4±1.6 mg/ml，术后10.3±1.3 mg/ml，P<0.05）。IR抑制剂PC-1的肌肉含量无显著变化。
IR含量增加，很可能受胰岛素水平调节，可能是病态肥胖患者接受减肥手术时胰岛素敏感性增加的一个原因。
