Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice
Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice
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DOI：
10.1172/jci7901
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发表时间：
2000-02-01
影响因子：
15.9
通讯作者：
Reitman, ML
中科院分区：
文献类型：
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作者：
Gavrilova, O;Marcus-Samuels, B;Reitman, ML
在脂肪萎缩性糖尿病中，缺乏脂肪与胰岛素抵抗和高血糖症有关。这与糖尿病与肥胖的通常联系形成鲜明对比。为了了解潜在的机制，我们将脂肪组织移植到患有严重脂肪萎缩性糖尿病的A-ZIP/F-1小鼠体内。野生型脂肪的移植逆转了高血糖症，显著降低了胰岛素水平，并改善了肌肉胰岛素敏感性，表明A-ZIP/F-1小鼠中的糖尿病是由缺乏脂肪组织引起的。A-ZIP/F-1表型的所有方面，包括摄食过多、肝脂肪变性和体肥大，均部分或完全逆转。然而，甘油三酯和FFA水平的改善是适度的。从宫旁和皮下部位提取的供体脂肪在逆转表型方面同样有效。移植的有益效果是剂量依赖性的，需要接近生理量的移植脂肪。将转基因脂肪移植到A-ZIP/F-1小鼠中是研究脂肪生理学以及脂肪组织与身体其余部分之间的代谢和内分泌通讯的新的强大技术。
In lipoatrophic diabetes, a lack of fat is associated with insulin resistance and hyperglycemia. This is in striking contrast to the usual association of diabetes with obesity. To understand the underlying mechanisms, we transplanted adipose tissue into A-ZIP/F-1 mice, which have a severe form of lipoatrophic diabetes. Transplantation of wild-type fat reversed the hyperglycemia, dramatically lowered insulin levels, and improved muscle insulin sensitivity, demonstrating that the diabetes in A-ZIP/F-1 mice is caused by the lack of adipose tissue. All aspects of the A-ZIP/F-1 phenotype including hyperphagia, hepatic steatosis, and somatomegaly were either partially or completely reversed. However, the improvement in triglyceride and FFA levels was modest. Donor fat taken from parametrial and subcutaneous sites was equally effective in reversing the phenotype. The beneficial effects of transplantation were dose dependent and required near-physiological amounts of transplanted fat. Transplantation of,genetically modified fat into A-ZIP/F-1 mice is a new and powerful technique for studying adipose physiology and the metabolic and endocrine communication between adipose tissue and the rest of the body.