Glucokinase gene locus transgenic mice are resistant to the development of obesity-induced type 2 diabetes
Glucokinase gene locus transgenic mice are resistant to the development of obesity-induced type 2 diabetes
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DOI：
10.2337/diabetes.50.3.622
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发表时间：
2001-03-01
期刊：
影响因子：
7.7
通讯作者：
Cherrington, AD
中科院分区：
文献类型：
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作者：
Shiota, M;Postic, C;Cherrington, AD
过表达整个葡萄糖激酶（GK）基因位点的转基因小鼠先前已被证明是轻度低血糖，并具有改善的葡萄糖耐受性。为了确定增加GK是否也可以预防或减少饮食诱导的肥胖动物的糖尿病，我们研究了给这些小鼠喂食高脂肪高简单碳水化合物低纤维饮食（HF饮食）30周的效果。正常小鼠和转基因小鼠对这种饮食的反应都是肥胖，并且具有相似的BMI（转基因小鼠和非转基因小鼠分别为5.3 +/- 0.1和5.0 +/- 0.1 kg/m2）。对照小鼠的血糖浓度随时间线性增加，在第30周达到17.0 +/- 1.3 mmol/l。相比之下，GK转基因小鼠的血糖在第15周仅上升至9.7 +/- 1.2 mmol/l，之后在第30周恢复至7.6 +/- 1.0 mmol/l。GK转基因动物的血浆胰岛素浓度（232 +/- 79 pmol/l）也低于对照动物（595 +/- 77 pmol/l），但血浆胰高血糖素浓度无差异。总之，这些数据表明，GK水平的增加显著减轻了与HF饮食喂养相关的高血糖症和高胰岛素血症的发展。
Transgenic mice that overexpress the entire glucokinase (GK) gene locus have been previously shown to be mildly hypoglycemic and to have improved tolerance to glucose. To determine whether increased GK might also prevent or diminish diabetes in diet-induced obese animals, we examined the effect of feeding these mice a high-fat high-simple carbohydrate low-fiber diet (HF diet) for 30 weeks. In response to this diet, both normal and transgenic mice became obese and had similar BMIs (5.3 +/- 0.1 and 5.0 +/- 0.1 kg/m(2) in transgenic and nontransgenic mice, respectively). The blood glucose concentration of the control mice increased linearly with time and reached 17.0 +/- 1.3 mmol/l at the 30th week. In contrast, the blood glucose of GK transgenic mice rose to only 9.7 +/- 1.2 mmol/l at the 15th week, after which it returned to 7.6 +/- 1.0 mmol/l by the 30th week. The plasma insulin concentration was also lower in the GK transgenic animals (232 +/- 79 pmol/l) than in the controls (595 +/- 77 pmol/l), but there was no difference in plasma glucagon concentrations. Together, these data indicate that increased GK levels dramatically lessen the development of both hyperglycemia and hyperinsulinemia associated with the feeding of an HF diet.