Antiobesity effect of diazoxide in obese Zucker rats
Antiobesity effect of diazoxide in obese Zucker rats
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DOI：
10.1016/s0026-0495(96)90287-5
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发表时间：
1996-03-01
影响因子：
9.8
通讯作者：
Pitukcheewanont, P
中科院分区：
文献类型：
--
作者：
Alemzadeh, R;Jacobs, W;Pitukcheewanont, P
高胰岛素血症和胰岛素抵抗是肥胖者的特征表现。在人类和实验动物中，肥胖都与胰岛素受体数量减少和胰岛素介导的葡萄糖处置减少有关，而对胰岛素的抗脂作用的敏感性没有改变。为了评价二氮嗪(DZ)对葡萄糖刺激的胰岛素释放的抑制作用，对7周龄的Zucker肥胖和瘦大鼠进行了研究。将肥胖和消瘦大鼠分为臭氧处理组(150 mg/kg/d)和对照组(C)。与C肥胖动物相比，DZ治疗的肥胖大鼠每公斤体重(BW)消耗的卡路里相似，但体重增加更少(P<；.01)。肥胖动物吸收后血浆游离脂肪酸(FFA)、胆固醇和甘油三酯显著高于瘦肉动物(P<；.01)。DZ治疗降低了肥胖动物的血浆甘油三酯水平(P<；.001)，但对游离脂肪酸或胆固醇浓度没有显著影响。与C肥胖大鼠相比，DZ肥胖大鼠在吸收后状态和糖耐量试验(GTT)时的血糖浓度显著降低(P<；.01)，尽管DZ处理的动物的血浆胰岛素浓度降低(P<；.01)。相比之下，DZ瘦身大鼠出现了糖耐量异常(P<；0.05)。与C肥胖大鼠相比，OZ肥胖大鼠的脂肪细胞对胰岛素降脂作用的敏感性和反应性显著降低(P<；.01)。此外，脂肪细胞特异性胰岛素受体结合力在OZ瘦和OZ肥胖动物中均增加(P<；.01)。伴随这两种类型的基础和胰岛素刺激的葡萄糖转运增加(P<；.01)。综上所述，DZ增加了胰岛素受体结合和葡萄糖转运，同时降低了高胰岛素血症和胰岛素对胰岛素降脂作用的敏感性。这种联合作用改善了肥胖大鼠的糖耐量，减少了体重增加，这意味着对肥胖症胰岛素代谢紊乱的药物修饰可能在治疗上是有益的。版权所有(C)1996年，由W.B.Saunders公司
Hyperinsulinism and insulin resistance are characteristic findings in obese subjects. Obesity in both humans and experimental animals is associated with a reduced number of insulin receptors and a decreased insulin mediated glucose disposal, whereas sensitivity to insulin's antilipolytic action is unaltered. To evaluate the antiobesity effect of diazoxide (DZ), an inhibitor of glucose-stimulated insulin release, 7-week-old Zucker obese and lean rats were studied. Obese and lean rats were grouped into OZ-treated (150 mg/kg/d) and control (C) groups. DZ-treated obese rats consumed similar amounts of calories per kilogram body weight (BW) compared with C obese animals, but gained less weight (P < .01). Postabsorptive plasma free fatty acids (FFA), cholesterol, and triglycerides were significantly higher in obese versus lean animals (P < .01). DZ treatment reduced plasma triglyceride levels in obese animals (P < .001), but had no significant effect on FFA or cholesterol concentrations. Plasma glucose concentrations in the postabsorptive state and during glucose tolerance tests (GTTs) were significantly lower in DZ obese versus C obese rats (P < .01) despite a decrease in plasma insulin concentrations in DZ-treated animals (P < .01). In contrast, DZ lean rats developed glucose intolerance (P < .05). Sensitivity and responsiveness to the antilipolytic effect of insulin in isolated adipocytes were significantly decreased in OZ obese as compared with C obese rats (P < .01). Moreover, adipocyte specific insulin receptor binding was increased in both OZ lean and OZ obese animals (P < .01). This was accompanied by increased basal and insulin-stimulated glucose transport in both genotypes (P < .01). In conclusion, DZ increased insulin receptor binding and glucose transport while decreasing hyperinsulinemia and insulin sensitivity to the antilipolytic action of insulin. This combined effect resulted in improved glucose tolerance and a decrease in weight gain in obese rats, implying that pharmacologic modification of the disturbed insulin metabolism of obesity may be therapeutically beneficial. Copyright (C) 1996 by W.B. Saunders Company