Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats.
作者： R. J. Perry , D. Zhang , X.-M. Zhang , J. L. Boyer , G. I. Shulman
关键词: Steatohepatitis 、 Type 2 diabetes 、 Insulin resistance 、 Nonalcoholic fatty liver disease 、 Protonophore 、 Internal medicine 、 Medicine 、 Steatosis 、 Endocrinology 、 Metabolic syndrome 、 Mitochondrion
摘要: Nonalcoholic fatty liver disease (NAFLD) is a major factor in the pathogenesis of type 2 diabetes (T2D) and nonalcoholic steatohepatitis (NASH). The mitochondrial protonophore 2,4 dinitrophenol (DNP) has beneficial effects on NAFLD, insulin resistance, obesity preclinical models but too toxic for clinical use. We developed controlled-release oral formulation DNP, called CRMP (controlled-release protonophore), that produces mild hepatic uncoupling. In rat models, reduced hypertriglyceridemia, steatosis, diabetes. It also normalized plasma transaminase concentrations, ameliorated fibrosis, improved protein synthetic function methionine/choline–deficient model NASH. Chronic treatment with was not associated any systemic toxicity. These data offer proof concept uncoupling may be safe effective therapy related epidemics metabolic syndrome, T2D,
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