Carantoni M, Abbasi F, Azhar S, Chen Y D, Klebanov M, Wang P W, Warmerdam F, Reaven G M
Stanford University School of Medicine, California, USA.
Diabetes. 1998 Feb;47(2):244-7. doi: 10.2337/diab.47.2.244.
The aim of this study was to test the hypothesis that plasma leptin concentrations contributed to the pathophysiology of NIDDM by decreasing both insulin-mediated glucose disposal and glucose-stimulated insulin secretion. The study was performed in 60 women with normal oral glucose tolerance. Differences in insulin-mediated glucose disposal were determined by comparing the steady-state plasma glucose (SSPG) concentrations attained at the end of a 180-min constant infusion of somatostatin, glucose, and insulin, while comparisons of glucose-stimulated insulin secretion were based on the incremental increase in insulin concentration 30 min after an oral glucose challenge (deltaIns) as compared with the fasting value. The results showed that the higher the fasting plasma leptin concentration, the greater the degree of insulin resistance (r = 0.47, P < 0.01). Furthermore, multiple regression analysis indicated that the relationship between leptin and SSPG was independent of age and degree of obesity as estimated by BMI. However, since the total integrated plasma insulin response was highly correlated with both SSPG (r = 0.80, P < 0.001) and leptin (r = 0.55, P < 0.01), multiple regression analysis was repeated, adding total insulin response to the model. When this was done, the significant relationship between leptin and SSPG disappeared, whereas both BMI (P < 0.03) and insulin response (P < 0.001) were correlated with SSPG. A significant relationship between leptin and deltaIns was seen, but it was a positive one (r = 0.31, P < 0.02), not a negative one as would be expected if circulating levels of leptin inhibited glucose-stimulated insulin secretion. Furthermore, multiple regression analysis could only confirm an independent relationship between deltaIns and SSPG, but not between deltaIns and leptin. The results of these studies do not support the view that circulating leptin has a primary effect on either insulin action or secretion in normal female volunteers. It seems more likely that chronic hyperinsulinemia in insulin-resistant individuals acts to increase adipose tissue leptin synthesis and secretion, leading to higher ambient leptin concentrations.
血浆瘦素浓度通过降低胰岛素介导的葡萄糖处置及葡萄糖刺激的胰岛素分泌，参与非胰岛素依赖型糖尿病（NIDDM）的病理生理过程。该研究在60名口服葡萄糖耐量正常的女性中进行。胰岛素介导的葡萄糖处置差异通过比较在持续输注生长抑素、葡萄糖和胰岛素180分钟结束时达到的稳态血浆葡萄糖（SSPG）浓度来确定，而葡萄糖刺激的胰岛素分泌比较则基于口服葡萄糖激发后30分钟胰岛素浓度相对于空腹值的增量增加（deltaIns）。结果显示，空腹血浆瘦素浓度越高，胰岛素抵抗程度越大（r = 0.47，P < 0.01）。此外，多元回归分析表明，瘦素与SSPG之间的关系独立于年龄和由体重指数（BMI）估算的肥胖程度。然而，由于总的血浆胰岛素综合反应与SSPG（r = 0.80，P < 0.001）和瘦素（r = 0.55，P < 0.01）均高度相关，因此重复进行多元回归分析，将总胰岛素反应加入模型。这样做时，瘦素与SSPG之间的显著关系消失，而BMI（P < 0.03）和胰岛素反应（P < 0.001）均与SSPG相关。观察到瘦素与deltaIns之间存在显著关系，但为正相关（r = 0.31，P < 0.02），而非如预期的负相关，即如果循环中的瘦素水平抑制葡萄糖刺激的胰岛素分泌的话。此外，多元回归分析仅能证实deltaIns与SSPG之间的独立关系，而非deltaIns与瘦素之间的独立关系。这些研究结果不支持循环瘦素对正常女性志愿者的胰岛素作用或分泌有主要影响这一观点。更有可能的情况似乎是，胰岛素抵抗个体中的慢性高胰岛素血症促使脂肪组织瘦素合成和分泌增加，导致周围瘦素浓度升高。
