ePrints@IIScePrints@IISc Home | About | Browse | Latest Additions | Advanced Search | Contact | Help

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.

[img] PDF
fulltext.pdf - Published Version
Restricted to Registered users only

Download (373Kb) | Request a copy
Official URL: http://www.springerlink.com/content/26278t1560283l...

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
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.ernet.in/id/eprint/21642

Actions (login required)

View Item View Item