Both maximal expression of selenoproteins and selenoprotein deficiency can promote development of type 2 diabetes-like phenotype in mice.

Abstract:

:Selenium (Se) is an essential trace element in mammals that has been shown to exert its function through selenoproteins. Whereas optimal levels of Se in the diet have important health benefits, a recent clinical trial has suggested that supplemental intake of Se above the adequate level potentially may raise the risk of type 2 diabetes mellitus. However, the molecular mechanisms for the effect of dietary Se on the development of this disease are not understood. In the present study, we examined the contribution of selenoproteins to increased risk of developing diabetes using animal models. C57BL/6J mice (n=6-7 per group) were fed either Se-deficient Torula yeast-based diet or diets supplemented with 0.1 and 0.4 parts per million Se. Our data show that mice maintained on an Se-supplemented diet develop hyperinsulinemia and have decreased insulin sensitivity. These effects are accompanied by elevated expression of a selective group of selenoproteins. We also observed that reduced synthesis of these selenoproteins caused by overexpression of an i(6)A(-) mutant selenocysteine tRNA promotes glucose intolerance and leads to a diabetes-like phenotype. These findings indicate that both high expression of selenoproteins and selenoprotein deficiency may dysregulate glucose homeostasis and suggest a role for selenoproteins in development of diabetes.

journal_name

Antioxid Redox Signal

authors

Labunskyy VM,Lee BC,Handy DE,Loscalzo J,Hatfield DL,Gladyshev VN

doi

10.1089/ars.2010.3526

subject

Has Abstract

pub_date

2011-06-15 00:00:00

pages

2327-36

issue

12

eissn

1523-0864

issn

1557-7716

journal_volume

14

pub_type

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