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Hyperglycemia, maturity-onset obesity, and insulin resistance in NONcNZO10/LtJ males, a new mouse model of type 2 diabetes.

Authors :
Cho YR
Kim HJ
Park SY
Ko HJ
Hong EG
Higashimori T
Zhang Z
Jung DY
Ola MS
Lanoue KF
Leiter EH
Kim JK
Source :
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2007 Jul; Vol. 293 (1), pp. E327-36.
Publication Year :
2007

Abstract

As a new mouse model of obesity-induced diabetes generated by combining quantitative trait loci from New Zealand Obese (NZO/HlLt) and Nonobese Nondiabetic (NON/LtJ) mice, NONcNZO10/LtJ (RCS10) male mice developed type 2 diabetes characterized by maturity onset obesity, hyperglycemia, and insulin resistance. To metabolically profile the progression to diabetes in preobese and obese states, a 2-h hyperinsulinemic euglycemic clamp was performed and organ-specific changes in insulin action were assessed in awake RCS10 and NON/LtJ (control) males at 8 and 13 wk of age. Prior to development of obesity and attendant increases in hepatic lipid content, 8-wk-old RCS10 mice developed insulin resistance in liver and skeletal muscle due to significant decreases in insulin-stimulated glucose uptake and GLUT4 expression in muscle. Transition to an obese and hyperglycemic state by 13 wk of age exacerbated insulin resistance in skeletal muscle, liver, and heart associated with organ-specific increases in lipid content. Thus, this polygenic mouse model of type 2 diabetes, wherein plasma insulin is only modestly elevated and obesity develops with maturity yet insulin action and glucose metabolism in skeletal muscle and liver are reduced at an early prediabetic age, should provide new insights into the etiology of type 2 diabetes.

Details

Language :
English
ISSN :
0193-1849
Volume :
293
Issue :
1
Database :
MEDLINE
Journal :
American journal of physiology. Endocrinology and metabolism
Publication Type :
Academic Journal
Accession number :
17616608
Full Text :
https://doi.org/10.1152/ajpendo.00376.2006