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Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes

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Abstract

Pancreatic β-cell dysfunction and insulin resistance are observed in type 2 diabetes. Under diabetic conditions, oxidative stress and ER stress are induced in various tissues, leading to activation of the JNK pathway. This JNK activation suppresses insulin biosynthesis and interferes with insulin action. Indeed, suppression of the JNK pathway in diabetic mice improves insulin resistance and ameliorates glucose tolerance. Thus, the JNK pathway plays a central role in pathogenesis of type 2 diabetes and may be a potential target for diabetes therapy.

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Abbreviations

DN:

Dominant-negative

ER:

Endoplasmic reticulum

IRS-1:

Insulin receptor substrate 1

JIP-1:

JNK-interacting protein-1

JNK:

c-Jun N-terminal kinase

PERK:

Pancreatic ER kinase (or PKR-like kinase)

PDX-1:

Pancreatic and duodenal homeobox factor-1

ROS:

Reactive oxygen species

TNF-α:

Tumor necrosis factor-α

XBP-1:

X-box-binding protein-1

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Authors and Affiliations

  1. Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Hideaki Kaneto, Taka-aki Matsuoka, Yoshihisa Nakatani, Dan Kawamori, Takeshi Miyatsuka, Munehide Matsuhisa & Yoshimitsu Yamasaki

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  1. Hideaki Kaneto
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Correspondence to Hideaki Kaneto.

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Kaneto, H., Matsuoka, Ta., Nakatani, Y. et al. Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes. J Mol Med 83, 429–439 (2005). https://doi.org/10.1007/s00109-005-0640-x

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  • DOI: https://doi.org/10.1007/s00109-005-0640-x

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