Saad M F, Khan A, Sharma A, Michael R, Riad-Gabriel M G, Boyadjian R, Jinagouda S D, Steil G M, Kamdar V
Department of Medicine, University of Southern California Medical School, Los Angeles 90024, USA.
Diabetes. 1998 Apr;47(4):544-9. doi: 10.2337/diabetes.47.4.544.
Whether insulin acutely regulates plasma leptin in humans is controversial. We examined the dosage-response and time-course characteristics of the effect of insulin on leptin in 10 men (age 42+/-2 years [mean+/-SE]; BMI 29.3+/-2.0 kg/m2). Each individual underwent four 9-h euglycemic clamps (insulin at 20, 40, 80, and 400 mU x m[-2] x min[-1) and a control saline infusion. Although plasma glucose and insulin levels remained constant, leptin diminished from 9.1+/-3.0 to 5.9+/-2.1 ng/ml (P < 0.001) by the end of the control experiment. Conversely, plasma leptin showed a dosage-dependent increase during the insulin infusions that was evident within 30-60 min. The insulin-induced increase in leptin was proportionately lower in obese insulin-resistant men. Free fatty acids (FFAs) decreased during insulin and did not change during saline infusions. ED50 (the dose producing half-maximal effect) for insulin's effect on leptin and FFA was similar (138+/-36 vs. 102+/-24 pmol/l, respectively; P=0.11). To further define the role of physiological insulinemia, we compared the effect of a very low dosage insulin infusion (10 mU x m[-2] x min[-1]) with that of a control saline infusion in another group of 10 men (mean age 39+/-3 years; BMI 27.1+/-1.0 kg/m2). Plasma leptin remained stable during that insulin infusion, but fell by 37+/-2% in the control experiment. Thus physiological insulinemia can acutely regulate plasma leptin. Insulin could mediate the effect of caloric intake on leptin and could be a determinant of its plasma concentration. Inadequate insulin-induced leptin production in obese and insulin-resistant subjects may contribute to the development or worsening of obesity.
胰岛素是否能急性调节人体血浆瘦素存在争议。我们研究了10名男性(年龄42±2岁[均值±标准误];体重指数29.3±2.0kg/m²)中胰岛素对瘦素作用的剂量反应和时间进程特征。每位受试者接受了四次9小时的正常血糖钳夹实验(胰岛素剂量分别为20、40、80和400mU·m⁻²·min⁻¹)以及一次生理盐水对照输注。尽管血浆葡萄糖和胰岛素水平保持恒定,但在对照实验结束时,瘦素从9.1±3.0ng/ml降至5.9±2.1ng/ml(P<0.001)。相反,在胰岛素输注期间,血浆瘦素呈剂量依赖性增加,在30 - 60分钟内即可明显看出。肥胖胰岛素抵抗男性中,胰岛素诱导的瘦素增加幅度相对较小。胰岛素输注期间游离脂肪酸(FFA)减少,生理盐水输注期间则无变化。胰岛素对瘦素和FFA作用的半数有效剂量(ED50)相似(分别为138±36和102±24pmol/l;P = 0.11)。为进一步明确生理性胰岛素血症的作用,我们在另一组10名男性(平均年龄39±3岁;体重指数27.1±1.0kg/m²)中比较了极低剂量胰岛素输注(10mU·m⁻²·min⁻¹)与生理盐水对照输注的效果。在该胰岛素输注期间,血浆瘦素保持稳定,但在对照实验中下降了37±2%。因此,生理性胰岛素血症可急性调节血浆瘦素。胰岛素可能介导热量摄入对瘦素的影响,并且可能是其血浆浓度的一个决定因素。肥胖和胰岛素抵抗受试者中胰岛素诱导的瘦素产生不足可能导致肥胖的发生或加重。