Molecular convergence of hexosamine biosynthetic pathway and ER stress leading to insulin resistance in L6 skeletal muscle cells

Srinivasan, V and Tatu, U and Mohan, V and Balasubramanyam, M (2009) Molecular convergence of hexosamine biosynthetic pathway and ER stress leading to insulin resistance in L6 skeletal muscle cells. In: Molecular and Cellular Biochemistry, 328 (1-2). pp. 217-224.

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Abstract

Augmentation of hexosamine biosynthetic pathway (HBP) and endoplasmic reticulum (ER) stress were independently related to be the underlying causes of insulin resistance. We hypothesized that there might be a molecular convergence of activated HBP and ER stress pathways leading to insulin resistance. Augmentation of HBP in L6 skeletal muscle cells either by pharmacological (glucosamine) or physiological (high-glucose) means, resulted in increased protein expression of ER chaperones (viz., Grp78, Calreticulin, and Calnexin), UDP-GlcNAc levels and impaired insulin-stimulated glucose uptake. Cells silenced for O-glycosyl transferase (OGT) showed improved insulin-stimulated glucose uptake (P < 0.05) but without any effect on ER chaperone upregulation. While cells treated with either glucosamine or high-glucose exhibited increased JNK activity, silencing of OGT resulted in inhibition of JNK and normalization of glucose uptake. Our study for the first time, demonstrates a molecular convergence of O-glycosylation processes and ER stress signals at the cross-road of insulin resistance in skeletal muscle.

Item Type:	Journal Article
Publication:	Molecular and Cellular Biochemistry
Publisher:	Springer
Additional Information:	Copyright of this article belongs to Springer.
Keywords:	Insulin resistance;Diabetes;HBP; ER stress;UDP-GlcNAc; OGT; RNAi;JNKG'lucose uptake;Skeletal muscle
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	06 Jan 2010 05:46
Last Modified:	19 Sep 2010 05:38
URI:	http://eprints.iisc.ac.in/id/eprint/21642

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