详细记录  
题名:High-Fat-Fed Obese Glutathione Peroxidase 1-Deficient Mice Exhibit Defective Insulin Secretion but Protection from Hepatic Steatosis and Liver Damage.
作者:MERRY TL; TRAN M; STATHOPOULOS M; WIEDE F; FAM BC; DODD GT; CLARKE I; WATT MJ; ANDRIKOPOULOS S; TIGANIS T;
来源:Antioxid Redox Signal. 2014 Mar 11. [ IF= 0.00 ] ]
URL :10.1089/ars.2013.5428
日期:20140408
摘要:Abstract Aims: Reactive oxygen species (ROS) such as H2O2 can promote signaling
through the inactivation of protein tyrosine phosphatases (PTPs). However, in
obesity, the generation of ROS exceeds the antioxidant reserve and can contribute
to the promotion of insulin resistance. Glutathione peroxidase 1 (Gpx1) is an
antioxidant enzyme that eliminates H2O2. Here, we have used Gpx1-/- mice to
assess the impact of oxidative stress on glucose homeostasis in the context of
obesity. Results: Gpx1-/- mice fed an obesogenic high-fat diet for 12 weeks
exhibited systemic oxidative stress and hyperglycemia, but had unaltered
whole-body insulin sensitivity, improved hepatic insulin signaling, and decreased
whole-body glucose production. High-fat-fed Gpx1-/- mice also exhibited decreased
hepatic steatosis and liver damage accompanied by decreased plasma insulin and
decreased glucose-induced insulin secretion. The decreased insulin secretion was
associated with reduced islet beta cell pancreatic and duodenal homeobox-1 (Pdx1)
and insulin content, elevated pancreatic PTP oxidation (including PTPN2
oxidation), and elevated signal transducer and activator of transcription 1
(STAT1) Y701 phosphorylation. Innovation and Conclusion: Taken together, these
results are consistent with H2O2 inactivating pancreatic PTPs (such as the STAT1
phosphatase PTPN2) for the promotion of STAT-1 signaling to suppress Pdx1
expression and differentiation and, consequently, reduce beta cell insulin
secretion. We propose that the decreased insulin secretion, in turn, results in
decreased hepatic lipogenesis and steatosis, attenuates liver damage, and
improves hepatic insulin signaling to suppress hepatic glucose production.
Limiting insulin secretion may help combat the development of hepatic steatosis
and liver damage in diet-induced obesity. Antioxid. Redox Signal. 00: 000-000.

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