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

Vyacheslav M. Labunskyy, Byung Cheon Lee, Diane E. Handy, Joseph Loscalzo, Dolph L. Hatfield, Vadim N. Gladyshev

Research output: Contribution to journalArticle

104 Citations (Scopus)

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 i6A- 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.

Original languageEnglish
Pages (from-to)2327-2336
Number of pages10
JournalAntioxidants and Redox Signaling
Volume14
Issue number12
DOIs
Publication statusPublished - 2011 Jun 15
Externally publishedYes

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Selenoproteins
Medical problems
Selenium
Type 2 Diabetes Mellitus
Phenotype
Nutrition
Diet
Cryptococcus
Glucose
Mammals
Glucose Intolerance
Hyperinsulinism
Trace Elements
Insurance Benefits
Inbred C57BL Mouse
Yeast
Insulin Resistance
Animals
Homeostasis
Animal Models

ASJC Scopus subject areas

  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Both maximal expression of selenoproteins and selenoprotein deficiency can promote development of type 2 diabetes-like phenotype in mice. / Labunskyy, Vyacheslav M.; Lee, Byung Cheon; Handy, Diane E.; Loscalzo, Joseph; Hatfield, Dolph L.; Gladyshev, Vadim N.

In: Antioxidants and Redox Signaling, Vol. 14, No. 12, 15.06.2011, p. 2327-2336.

Research output: Contribution to journalArticle

Labunskyy, Vyacheslav M. ; Lee, Byung Cheon ; Handy, Diane E. ; Loscalzo, Joseph ; Hatfield, Dolph L. ; Gladyshev, Vadim N. / Both maximal expression of selenoproteins and selenoprotein deficiency can promote development of type 2 diabetes-like phenotype in mice. In: Antioxidants and Redox Signaling. 2011 ; Vol. 14, No. 12. pp. 2327-2336.
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