Insulin secretion, peripheral insulin sensitivity and insulin-receptor binding in subjects with different degrees of obesity
Insulin secretion, peripheral insulin sensitivity and insulin-receptor binding in subjects with different degrees of obesity
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DOI：
10.1016/s1262-3636(07)70138-6
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发表时间：
2004-11-01
影响因子：
7.2
通讯作者：
Koev, DJ
中科院分区：
文献类型：
--
作者：
Borissova, AM;Tankova, TI;Koev, DJ
目的：本研究的目的是探讨不同程度肥胖者的胰岛素分泌、胰岛素受体结合和外周血胰岛素敏感性。方法：36例糖耐量正常的肥胖者和40例正常体重的健康者参加了这项研究。外周血胰岛素敏感性测定采用正常血高胰岛素钳夹技术，和胰岛素受体结合循环单核细胞。结果：与正常体重组相比，1度肥胖组每细胞胰岛素受体总数（p < 0.0001）和高亲和力（p < 0.01）明显减少，而胰岛素受体亲和力（p < 0.01）明显增加。与对照组相比，II度肥胖受试者的每个细胞的总受体（p < 0.0001）和高亲和力受体（p < 0.001）数量也显著减少，胰岛素受体亲和力增加（p < 0.001）。I和II度肥胖受试者的受体数量显著减少，伴随着胰岛素受体亲和力的增加;因此，其胰岛素受体结合保持与对照组相似。与对照组相比，患有III度肥胖症的受试者在总胰岛素受体和高亲和力胰岛素受体的数量上均呈现显著降低（p < 0.0001），并且胰岛素受体亲和力降低。因此，与对照组相比，特异性结合胰岛素的百分比显著降低（p < 0.01）。肥胖受试者的胰岛素抵抗与继发性高胰岛素血症相关，这在I和II度肥胖受试者中存在;而在严重肥胖受试者中观察到β细胞分泌能力耗尽。我们认为III度肥胖似乎是2型糖尿病的危险因素，因为胰岛素敏感性的改变，胰岛素受体结合和β细胞分泌与糖尿病患者中报道的非常相似。
Objectives: The aim of the present study was to investigate insulin secretion, insulin-receptor binding and peripheral insulin sensitivity in subjects with different degrees of obesity.Methods: 36 obese subjects with normal glucose tolerance and different degrees of obesity and 40 healthy normal-weight subjects participated in the study. Peripheral insulin sensitivity was measured by using the euglycaemic hyperinsulinaemic clamp technique, and insulin-receptor binding-on circulating mononuclear blood cells. Insulin secretion was studied during intravenous tolbutamide test.Results: The subjects with 1 degree of obesity demonstrated a significant decrease in the number of total (p < 0.0001) and high-affinity (p < 0.01) insulin receptors per cell, as well as significantly higher insulin receptor affinity (p < 0.01) as compared to the normal-weight subjects. The subjects with II degree of obesity also demonstrated a significant decrease in the number of total (p < 0.0001) and high-affinity receptors (p < 0.001) per cell as well as an increase (p < 0.001) in insulin-receptor affinity as compared to the controls. The significantly decreased receptor number in the subjects with I and II degree of obesity was accompanied by an increase in insulin receptor affinity; thus their insulin-receptor binding being maintained similar to the controls. The subjects with III degree obesity presented a significant decrease (p < 0.0001) in the number of both the total and high-affinity insulin receptors as well as a reduction in insulin receptor affinity as compared to the controls. Therefore the percentage of specifically bound insulin was significantly lower (p < 0.01) as compared to that of the control group. Insulin resistance in the obese subjects is associated with secondary hyperinsulinaemia, which is present in subjects with I and II degree of obesity; while in severely obese subjects exhaustion of beta-cell secretory capacity is observed.Conclusion: We consider that III degree of obesity appears to be a risk factor for type 2 diabetes mellitus as the alterations in insulin sensitivity, insulin-receptor binding and beta-cell secretion are quite similar to the reported in diabetic patients.