HIGH-FAT DIET-INDUCED HYPERGLYCEMIA - PREVENTION BY LOW-LEVEL EXPRESSION OF A GLUCOSE-TRANSPORTER (GLUT4) MINIGENE IN TRANSGENIC MICE
HIGH-FAT DIET-INDUCED HYPERGLYCEMIA - PREVENTION BY LOW-LEVEL EXPRESSION OF A GLUCOSE-TRANSPORTER (GLUT4) MINIGENE IN TRANSGENIC MICE
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DOI：
10.1073/pnas.92.8.3096
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发表时间：
1995-04-11
影响因子：
11.1
通讯作者：
EZAKI, O
中科院分区：
文献类型：
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作者：
IKEMOTO, S;THOMPSON, KS;EZAKI, O
高脂肪摄入导致肥胖有助于非胰岛素依赖型糖尿病（NIDDM， 2型）的发展。同样，喂食高脂肪（红花油）饮食的小鼠也会出现血糖控制缺陷、高血糖和肥胖。为了评估适度增加GLUT4（胰岛素反应性葡萄糖转运蛋白）表达对脂肪喂养引起的血糖控制受损的影响，研究人员给含有GLUT4小基因的转基因小鼠喂食高脂肪饮食。在转基因小鼠中，低水平的组织特异性（心脏、骨骼肌和脂肪组织）表达GLUT4 miniigene可以防止由脂肪喂养引起的血糖控制损伤和伴随的高血糖，但不能防止肥胖。因此，在小鼠模型中，组织中GLUT4水平的小幅增加（小于或等于2倍）可以防止糖尿病状态的主要症状，这提示了干预治疗NIDDM的可能目标。
High-fat intake leading to obesity contributes to the development of non-insulin-dependent diabetes mellitus (NIDDM, type 2). Similarly, mice fed a high-fat (safflower oil) diet develop defective glycemic control, hyperglycemia, and obesity, To assess the effect of a modest increase in the expression of GLUT4 (the insulin-responsive glucose transporter) on impaired glycemic control caused by fat feeding, transgenic mice harboring a GLUT4 minigene were fed a high-fat diet. Low-level tissue-specific (heart, skeletal muscle, and adipose tissue) expression of the GLUT4 minigene in transgenic mice prevented the impairment of glycemic control and accompanying hyperglycemia, but not obesity, caused by fat feeding. Thus, a small increase (less than or equal to 2-fold) in the tissue level of GLUT4 prevents a primary symptom of the diabetic state in a mouse model, suggesting a possible target for intervention in the treatment of NIDDM.