High-Fat-Fed Obese Glutathione Peroxidase 1-Deficient Mice Exhibit Defective Insulin Secretion but Protection from Hepatic Steatosis and Liver Damage

Abstract

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 β 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.