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ER stress in rodent islets of Langerhans is concomitant with obesity and β-cell compensation but not with β-cell dysfunction and diabetes

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posted on 11.12.2013, 14:25 by O. Omikorede, C. Qi, T. Gorman, P. Chapman, A. Yu, D.M. Smith, Terence P. Herbert
Objective: The objective of this study was to determine whether ER stress correlates with b-cell dysfunction in obesity-associated diabetes. Methods: Quantitative RT-PCR and western blot analysis were used to investigate changes in the expression of markers of ER stress, the unfolded protein response (UPR) and β-cell function in islets isolated from (1) non-diabetic Zucker obese (ZO) and obese female Zucker diabetic fatty (fZDF) rats compared with their lean littermates and from (2) high-fat-diet-fed fZDF rats (HF-fZDF), to induce diabetes, compared with age-matched non-diabetic obese fZDF rats. Results: Markers of an adaptive ER stress/UPR and β-cell function are elevated in islets isolated from ZO and fZDF rats compared with their lean littermates. In islets isolated from HF-fZDF rats, there was no significant change in the expression of markers of ER stress compared with age matched, obese, non-diabetic fZDF rats. Conclusions: These results provide evidence that obesity-induced activation of the UPR is an adaptive response for increasing the ER folding capacity to meet the increased demand for insulin. As ER stress is not exacerbated in high-fat-diet-induced diabetes, we suggest that failure of the islet to mount an effective adaptive UPR in response to an additional increase in insulin demand, rather than chronic ER stress, may ultimately lead to β-cell failure and hence diabetes.

Funding

We thank Astra Zeneca and the Biotechnology and Biological Sciences Research Council for funding this project. OO was supported by a BBSRC/AstraZeneca CASE studentship.

History

Citation

Nutrition and Diabetes, 2013, 3, e93

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Cell Physiology and Pharmacology

Version

VoR (Version of Record)

Published in

Nutrition and Diabetes

Publisher

Nature Publishing Group

eissn

2044-4052

Copyright date

2013

Available date

11/12/2013

Publisher version

http://www.nature.com/nutd/journal/v3/n10/full/nutd201335a.html

Language

en

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