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Autophagy regulates insulin resistance following endoplasmic reticulum stress in diabetes

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Abstract

Autophagy is a kind of cell biological process that maintains the cell’s energy level under nutrient-poor conditions, regulates the turnover of abnormal or aged proteins, and disposes of dysfunctional organelles. The autophagy system is activated as a novel signaling pathway in response to endoplasmic reticulum stress (ER stress)-induced insulin resistance (IR). Defective autophagy may be closely related to insulin resistance. There are at least three mechanistically distinct arms of ER stress that regulate the expression of key genes which not only function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids, and lipids. ER stress-stimulated insulin resistance is mediated by the autophagy-dependent process. In settings of chronic ER stress, the associated autophagy may contribute to pathophysiological processes involved in a number of prevalent diseases, including diabetes. Whether autophagy plays a protective or harmful role in diabetes awaits further analysis. In this review, we will summarize the current knowledge about the emerging role of autophagy in ER stress-induced insulin resistance. Strategies to take advantage of the potential protective effect of autophagy remain important in the overall treatment of insulin resistance and type 2 diabetes.

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Abbreviations

ER:

Endoplasmic reticulum

ER stress:

Endoplasmic reticulum stress

IR:

Insulin resistance

IRE1:

Inositol requiring kinase 1

PERK:

PKR-like ER kinase

ATF6:

Activating transcription factor 6

JNK:

c-Jun N-terminal kinase

eIF2α:

Eukaryotic translation initiation factor-2α

BiP:

Immunoglobulin heavy chain binding protein

mTOR:

Mammalian target of rapamycin

LC3:

Microtubule-associated protein 1 light chain 3

3-MA:

3-Methyladenine

TRAF2:

Tumor necrosis factor receptor-associated factor 2

IRS1:

Insulin receptor substrate 1

Atg:

Autophagy-related

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81370929), a grant from the Novo Nordisk China Diabetes Young Scientific Talent Research Funding (2013), the Research Fund for the clinical medicine of Chinese Medical Association (13040670452), the Science Foundation of the Education Department of Heilongjiang Province (No.12531316), and a grant from the Health Department of Heilongjiang Province (2012-540).

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Authors and Affiliations

  1. Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China

    Ning Zhang, Ming-ming Cao, Han Liu, Guang-ying Xie & Yan-bo Li

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  1. Ning Zhang
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Correspondence to Yan-bo Li.

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Zhang, N., Cao, Mm., Liu, H. et al. Autophagy regulates insulin resistance following endoplasmic reticulum stress in diabetes. J Physiol Biochem 71, 319–327 (2015). https://doi.org/10.1007/s13105-015-0384-1

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