Soluble epoxide hydrolase (sEH) is an enzyme involved in the metabolism of endogenous inflammatory and anti-apoptotic mediators. In the present study, we determined the effects of the inhibition of sEH on glucose homeostasis and islet damage in mice treated with streptozotocin (STZ), a model of chemical-induced diabetes. STZ increased daily water intake and decreased visceral (spleen and pancreas) weight in mice; sEH inhibition in STZ mice decreased water intake, but did not affect visceral weight. Hyperglycemia induced by STZ treatment in mice was attenuated by inhibiting sEH. The beneficial effects of sEH inhibition were accompanied, after 2 and 4 weeks of initial administration, by improving glucose tolerance. In contrast, sEH inhibition did not affect insulin tolerance. Using LC/MS analysis, neither STZ nor STZ plus sEH inhibition affected pancreatic and plasma ratios of epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), an index of EETs levels. Western blot analysis showed that mouse cytochrome P450 (CYP) 2C enzymes are the major epoxygenases in islets. On day 5 after initial STZ treatment, STZ induced islet cell apoptosis, while sEH inhibition in STZ mice significantly reduced islet cell apoptosis. These studies provide pharmacological evidence that inhibiting sEH activity provides significant protection against islet beta-cell damage and improves glucose homeostasis in STZ-induced diabetes. (C) 2012 Elsevier Inc. All rights reserved.
Georgia Hlth Sci Univ, Dept Physiol, Augusta, GA 30912 USA;Chinese Acad Sci, Xinjiang Key Lab Plant Resources & Natl Prod Chem, Xinjiang Tech Inst Phys & Chem, Urumqi 830011, Peoples R China;Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA; Univ Calif Davis, UCD Canc Ctr, Davis, CA 95616 USA;Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA; Hubei Polytech Univ, Huangshi Cent Hosp, Huangshi 435000, Hubei Province, Peoples R China;Huangshi Key Lab Kidney & Metab Dis, Huangshi 435000, Hubei Province, Peoples R China; Georgia Hlth Sci Univ, Ctr Biotechnol & Genom Med, Augusta, GA 30912 USA
Chen Lingdan,Fan Cheng,Zhang Yi,et al. Beneficial effects of inhibition of soluble epoxide hydrolase on glucose homeostasis and islet damage in a streptozotocin-induced diabetic mouse model[J]. PROSTAGLANDINS & OTHER LIPID MEDIATORS,2013,104(SI):42-48.