Involvement of Oxidative Stress and the JNK Pathway in Glucose Toxicity

Overview

Journal Rev Diabet Stud

Specialty Endocrinology

Date 2007 May 12

PMID 17491701

Citations 21

Authors

Hideaki Kaneto

Yoshihisa Nakatani

Dan Kawamori

Takeshi Miyatsuka

Taka-Aki Matsuoka

Affiliations

Soon will be listed here.

Abstract

The hallmark of type 2 diabetes is pancreatic beta-cell dysfunction and insulin resistance. Normal beta-cells can compensate for insulin resistance by increasing insulin secretion, but insufficient compensation leads to the onset of glucose intolerance. Once hyperglycemia becomes apparent, beta-cell function gradually deteriorates and insulin resistance becomes aggravated. Such phenomena are collectively called "glucose toxicity". Under diabetic conditions, oxidative stress is induced and the JNK pathway is activated, which is involved in "glucose toxicity". Activation of the JNK pathway suppresses insulin biosynthesis and interferes with insulin action. Indeed, suppression of the JNK pathway in diabetic mice improves insulin resistance and ameliorates glucose tolerance. Consequently, the JNK pathway plays a crucial role in the progression of pancreatic beta-cell dysfunction and insulin resistance and thus could be a potential therapeutic target for the "glucose toxicity" found in diabetes.

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