GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes
GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes
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DOI：
10.1038/nm1097-1096
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发表时间：
1997-10-01
期刊：
影响因子：
82.9
通讯作者：
Charron, MJ
中科院分区：
文献类型：
--
作者：
Stenbit, AE;Tsao, TS;Charron, MJ
GLUT 4是胰岛素敏感的葡萄糖转运蛋白，在餐后葡萄糖代谢中起重要作用。改变的GLUT I活性被认为是导致肥胖和糖尿病中肌肉和脂肪组织中葡萄糖摄取减少的因素之一。为了评估GLUT 4表达对全身葡萄糖稳态的影响，我们通过同源重组破坏了小鼠GLUT 4基因。突变（GLUT 4（+/-））杂合子雄性小鼠脂肪组织和骨骼肌中GLUT 4表达降低。这种GLUT 4表达的减少不会导致肥胖，但会导致血清葡萄糖和胰岛素增加、肌肉葡萄糖摄取减少、高血压以及心脏和肝脏中的糖尿病组织病理学，与患有非胰岛素依赖型糖尿病（NIDDM）的人相似。雄性GLUT 4（+/-）小鼠代表了用于研究无肥胖相关并发症的NIDDM发展的良好模型。
GLUT4, the insulin-responsive glucose transporter, plays an important role in postprandial glucose disposal. Altered GLUT I activity is suggested to be one of the factors responsible for decreased glucose uptake in muscle and adipose tissue in obesity and diabetes. To assess the effect of GLUT4 expression on whole-body glucose homeostasis, we disrupted the murine GLUT4 gene by homologous recombination. Male mice heterozygous for the mutation (GLUT4(+/-)) exhibited a decrease in GLUT4 expression in adipose tissue and skeletal muscle. This decrease in GLUT4 expression did not result in obesity but led to increased serum glucose and insulin, reduced muscle glucose uptake, hypertension, and diabetic histopathologies in the heart and liver similar to those of humans with non-insulin-dependent diabetes mellitus (NIDDM). The male GLUT4(+/-) mice represent a good model for studying the development of NIDDM without the complications associated with obesity.