详细记录  
题名:Alterations of Pancreatic Islet Structure, Metabolism and Gene Expression in Diet-Induced Obese C57BL/6J Mice.
作者:ROAT R; RAO V; DOLIBA NM; MATSCHINSKY FM; TOBIAS JW; GARCIA E; AHIMA RS; IMAI Y;
来源:PLoS One. 2014 Feb 5;9(2):e86815. doi: 10.1371/journal.pone.0086815. eCollection [ IF= 3.73 ] ]
URL :10.1371/journal.pone.0086815
日期:20140317
摘要:The reduction of functional beta cell mass is a key feature of type 2 diabetes.
Here, we studied metabolic functions and islet gene expression profiles of
C57BL/6J mice with naturally occurring nicotinamide nucleotide transhydrogenase
(NNT) deletion mutation, a widely used model of diet-induced obesity and
diabetes. On high fat diet (HF), the mice developed obesity and hyperinsulinemia,
while blood glucose levels were only mildly elevated indicating a substantial
capacity to compensate for insulin resistance. The basal serum insulin levels
were elevated in HF mice, but insulin secretion in response to glucose load was
significantly blunted. Hyperinsulinemia in HF fed mice was associated with an
increase in islet mass and size along with higher BrdU incorporation to beta
cells. The temporal profiles of glucose-stimulated insulin secretion (GSIS) of
isolated islets were comparable in HF and normal chow fed mice. Islets isolated
from HF fed mice had elevated basal oxygen consumption per islet but failed to
increase oxygen consumption further in response to glucose or carbonyl
cyanide-4-trifluoromethoxyphenylhydrazone (FCCP). To obtain an unbiased
assessment of metabolic pathways in islets, we performed microarray analysis
comparing gene expression in islets from HF to normal chow-fed mice. A few genes,
for example, those genes involved in the protection against oxidative stress
(hypoxia upregulated protein 1) and Pgc1alpha were up-regulated in HF islets. In
contrast, several genes in extracellular matrix and other pathways were
suppressed in HF islets. These results indicate that islets from C57BL/6J mice
with NNT deletion mutation develop structural, metabolic and gene expression
features consistent with compensation and decompensation in response to HF diet.

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