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Whole body irradiation induces diabetes and adipose insulin resistance in nonhuman primates

Bacarella, N, Ruggiero, A, Davis, AT, Uberseder, B, Davis, MA, Bracy, DP, Wasserman, DH, Cline, JM, Sherrill, C and Kavanagh, K 2020 , 'Whole body irradiation induces diabetes and adipose insulin resistance in nonhuman primates' , International Journal of Radiation Oncology Biology Physics, vol. 106, no. 4 , pp. 878-886 , doi: 10.1016/j.ijrobp.2019.11.034.

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Abstract

Purpose: Diabetes mellitus is a delayed effect of radiation exposure in human and nonhuman primates. Diabetes mellitus is characterized by peripheral tissue insulin resistance, and as a result, irradiation exposure may cause important changes in insulin-sensitive tissues such as muscle and adipose.Methods and materials: We prospectively investigated changes in response to irradiation (4 Gy whole body exposure) in 16 male rhesus macaques. We evaluated changes in body composition and glycemic control for 2 years. Insulin responsiveness, lipolysis, inflammation, and fibrosis were evaluated at study end.Results: Irradiated animals accumulate less fat and significantly increased percent glycation of hemoglobin A1c over time, such that 40% of irradiated monkeys had values that define them as diabetic at 2 years. Subcutaneous (SQ) adipose tissue was insulin resistant, as evidenced by reduced phosphorylation of the insulin receptor substrate-1 in response to insulin challenge and had increased basal lipolysis despite comparable insulin exposures to control animals. Irradiated SQ adipose tissue had more macrophage infiltration and adipocytes were larger. The observed hypertrophy was associated with decreased glycemic control and macrophage infiltration correlated with decreased adiponectin, signifying that inflammation is associated with worsening health. No evidence of SQ adipose fibrosis was detected.Conclusions: Our study is the first to prospectively illustrate that sublethal irradiation exposures directly propagate metabolic disease in the absence of obesity in nonhuman primates and implicate SQ adipose dysfunction as a target tissue.

Item Type: Article
Authors/Creators:Bacarella, N and Ruggiero, A and Davis, AT and Uberseder, B and Davis, MA and Bracy, DP and Wasserman, DH and Cline, JM and Sherrill, C and Kavanagh, K
Journal or Publication Title: International Journal of Radiation Oncology Biology Physics
Publisher: Elsevier, Inc
ISSN: 0360-3016
DOI / ID Number: 10.1016/j.ijrobp.2019.11.034
Copyright Information:

Copyright 2019 Elsevier Inc.

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