Molecular and Cellular Biochemistry

, Volume 328, Issue 1, pp 217–224

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

  • V. Srinivasan
  • U. Tatu
  • V. Mohan
  • M. Balasubramanyam
Article

DOI: 10.1007/s11010-009-0092-7

Cite this article as:
Srinivasan, V., Tatu, U., Mohan, V. et al. Mol Cell Biochem (2009) 328: 217. doi:10.1007/s11010-009-0092-7
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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.

Keywords

Insulin resistanceDiabetesHBPER stressUDP-GlcNAcOGTRNAiJNKGlucose uptakeSkeletal muscle

Supplementary material

11010_2009_92_MOESM1_ESM.pdf (33 kb)
(PDF 33 kb)

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • V. Srinivasan
    • 1
  • U. Tatu
    • 2
  • V. Mohan
    • 1
  • M. Balasubramanyam
    • 1
  1. 1.Department of Cell and Molecular BiologyMadras Diabetes Research Foundation, Dr. Mohan’s Diabetes Specialities CenterChennaiIndia
  2. 2.Department of BiochemistryIndian Institute of ScienceBangaloreIndia