Review

Involvement of Oxidative Stress and the JNK Pathway in Glucose Toxicity

Hideaki Kaneto, Yoshihisa Nakatani, Dan Kawamori, Takeshi Miyatsuka, Taka-aki Matsuoka

Keywords: diabetes, insulin resistance, insulin biosynthesis, oxidative stress, JNK pathway

Abstract

The hallmark of type 2 diabetes is pancreatic β-cell dysfunction and insulin resistance. Normal β-cells can compensate for insulin resistance by increasing insulin secretion, but insufficient compensation leads to the onset of glucose intolerance. Once hyperglycemia becomes apparent, β-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 β-cell dysfunction and insulin resistance and thus could be a potential therapeutic target for the "glucose toxicity" found in diabetes.

Fulltext: HTML , PDF (364KB)

This article has been cited by other articles:

	Obesity, metabolic syndrome, adipocytes and vascular function: A holistic viewpoint Achike FI, To NH, Wang H, Kwan CY Clin Exp Pharmacol Physiol 2011. 38(1):1-10
	Role of the transcriptional factor C/EBPβ in free fatty acid-elicited β-cell failure Plaisance V, Perret V, Favre D, Abderrahmani A, Yang JY, Widmann C, Regazzi R Mol Cell Endocrinol 2009. 305(1-2):47-55
	The effects of taurine, taurine homologs and hypotaurine on cell and membrane antioxidative system alterations caused by type 2 diabetes in rat erythrocytes Gossai D, Lau-Cam CA Adv Exp Med Biol 2009. 643:359-368
	Chromium (VI) induces insulin resistance in 3T3-L1 adipocytes through elevated reactive oxygen species generation Ge X, Liu Z, Qi W, Shi X, Zhai Q Free Radic Res 2008. 42(6):554-563
	Peripheral blood gene expression profiling for cardiovascular disease assessment Aziz H, Zaas A, Ginsburg GS Genomic Med 2007. 1(3-4):105-112
	Type 2 Diabetes - Failure, Blame and Guilt in the Adoption of Insulin Therapy Phillips P Rev Diabet Stud 2005. 2(1):35-39
	Tolerance Induction and Endogenous Regeneration of Pancreatic Beta-Cells in Established Autoimmune Diabetes Sia C, Homo-Delarche F Rev Diabet Stud 2004. 1(4):198-206