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题名:Manganese supplementation protects against diet-induced diabetes in wild type mice by enhancing insulin secretion.
作者:LEE SH; JOUIHAN HA; COOKSEY RC; JONES D; KIM HJ; WINGE DR; MCCLAIN DA;
来源:Endocrinology. 2013 Mar;154(3):1029-38. doi: 10.1210/en.2012-1445. Epub 2013 Jan [ IF= 4.46 ] ]
URL :10.1210/en.2012-1445
日期:20130330
摘要:Mitochondrial dysfunction is both a contributing mechanism and complication of
diabetes, and oxidative stress contributes to that dysfunction. Mitochondrial
manganese-superoxide dismutase (MnSOD) is a metalloenzyme that provides
antioxidant protection. We have previously shown in a mouse model of hereditary
iron overload that cytosolic iron levels affected mitochondrial manganese
availability, MnSOD activity, and insulin secretion. We therefore sought to
determine the metallation status of MnSOD in wild-type mice and whether altering
that status affected beta-cell function. 129/SvEVTac mice given supplemental
manganese exhibited a 73% increase in hepatic MnSOD activity and increased
metallation of MnSOD. To determine whether manganese supplementation offered
glucose homeostasis under a situation of beta-cell stress, we challenged C57BL/6J
mice, which are more susceptible to diet-induced diabetes, with a high-fat diet
for 12 weeks. Manganese was supplemented or not for the final 8 weeks on that
diet, after which we examined glucose tolerance and the function of isolated
islets. Liver mitochondria from manganese-injected C57BL/6J mice had similar
increases in MnSOD activity (81%) and metallation as were seen in 129/SvEVTac
mice. The manganese-treated group fed high fat had improved glucose tolerance
(24% decrease in fasting glucose and 41% decrease in area under the glucose
curve), comparable with mice on normal chow and increased serum insulin levels.
Isolated islets from the manganese-treated group exhibited improved insulin
secretion, decreased lipid peroxidation, and improved mitochondrial function. In
conclusion, MnSOD metallation and activity can be augmented with manganese
supplementation in normal mice on normal chow, and manganese treatment can
increase insulin secretion to improve glucose tolerance under conditions of
dietary stress.

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