Troglitazone action is independent of adipose tissue
Troglitazone action is independent of adipose tissue
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DOI：
10.1172/jci119839
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发表时间：
1997-12-01
影响因子：
15.9
通讯作者：
Graves, RA
中科院分区：
文献类型：
--
作者：
Burant, CF;Sreenan, S;Graves, RA
我们研究了曲格列酮对aP2/DTA小鼠的抗糖尿病作用，通过白喉毒素A链的脂肪特异性表达几乎消除了aP2/DTA小鼠的白色和棕色脂肪。aP2/DTA小鼠血清瘦素水平明显降低，且嗜食，但未出现体重增加，对照组小鼠出现高脂血症、高血糖症和高胰岛素血症，提示胰岛素抵抗型糖尿病。经曲格列酮治疗后，高血糖症状得到缓解，对腹腔注射葡萄糖的耐受性恢复正常，升高的胰岛素水平明显降低，曲格列酮还显著降低血清胆固醇水平。aP2/DTA小鼠血清甘油三酯的降低是由于VLDL-和ldl -相关甘油三酯的显著降低。在骨骼肌中，与对照组相比，aP2/DTA小鼠的甘油三酯水平降低，但糖原水平升高，在野生型小鼠中，曲格列酮治疗降低了骨骼肌，但没有降低肝脏甘油三酯，增加了肝脏和肌肉糖原含量。曲格列酮可降低aP2/DTA小鼠肌糖原含量，但不影响肌肉甘油三酯水平，肝脏过氧化物酶体增殖物激活受体γ mRNA水平略有升高，曲格列酮治疗后无明显变化，说明无显著脂肪沉积的动物可发生胰岛素抵抗和糖尿病。此外，曲格列酮可以改变葡萄糖和脂质代谢独立于其对脂肪组织的影响。
We have investigated the antidiabetic action of troglitazone in aP2/DTA mice, whose white and brown fat was virtually eliminated by fat-specific expression of diphtheria toxin A chain. aP2/DTA mice had markedly suppressed serum leptin levels and were hyperphagic, but did not gain excess weight, aP2/DTA mice fed a control diet were hyperlipidemic, hyperglycemic, and had hyperinsulinemia indicative of insulin-resistant diabetes, Treatment with troglitazone alleviated the hyperglycemia, normalized the tolerance to intraperitoneally injected glucose, and significantly decreased elevated insulin levels, Troglitazone also markedly decreased the serum levels of cholesterol, triglycerides, and free fatty acids both in wild-type and aP2/DTA mice, The decrease in serum triglycerides in aP2/DTA mice was due to a marked reduction in VLDL- and LDL-associated triglyceride. In skeletal muscle, triglyceride levels were decreased in aP2/DTA mice compared with controls, but glycogen levels were increased, Troglitazone treatment decreased skeletal muscle, but not hepatic triglyceride and increased hepatic and muscle glycogen content: in wild-type mice. Troglitazone deer-eased muscle glycogen content in aP2/DTA mice without affecting muscle triglyceride levels, The levels of peroxisomal proliferator-activated receptor gamma mRNA in liver increased slightly in aP2/DTA mice and were not changed by troglitazone treatment, The results demonstrate that insulin resistance and diabetes can occur in animals without significant adipose deposits. Furthermore, troglitazone can alter glucose and lipid metabolism independent of its effects on adipose tissue.