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. Molecular and Cellular Biochemistry, 328 (1-2). pp. 217-24. ISSN 0300-8177

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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:Article
Official URL/DOI:http://dx.doi.org/10.1007/s11010-009-0092-7
Uncontrolled Keywords:hexosamine biosynthetic pathway ;ER stress ;insulin resistance
Subjects:Biochemistry,Cell and Molecular Signalling > Molecular Aspects-Insulin Resistence
Biochemistry,Cell and Molecular Signalling > Molecular Pathology-Diabetes
Diabetes > Diabetes Research
Divisions:Department of Diabetology
Department of Advanced Research Biochemistry
ID Code:52
Deposited By:INVALID USER
Deposited On:06 Oct 2009 15:52
Last Modified:19 Oct 2009 12:27

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