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- Title
Glucokinase gene locus transgenic mice are resistant to the development of obesity-induced type 2 diabetes.
- Authors
Shiota, Masakazu; Shiota, M; Postic, C; Fujimoto, Y; Jetton, T L; Dixon, K; Pan, D; Grimsby, J; Grippo, J F; Magnuson, M A; Cherrington, A D
- Abstract
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/m2 in transgenic and non-transgenic 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.
- Subjects
FOOD of animal origin -- Fat content; LABORATORY mice; BLOOD sugar analysis; RNA metabolism; OBESITY complications; ANIMAL experimentation; COMPARATIVE studies; DISEASE susceptibility; FAT content of food; GENE mapping; GENES; GLUCAGON; INSULIN; LIVER; RESEARCH methodology; MEDICAL cooperation; MICE; TYPE 2 diabetes; OBESITY; REFERENCE values; RESEARCH; TRANSFERASES; EVALUATION research
- Publication
Diabetes, 2001, Vol 50, Issue 3, p622
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.50.3.622