期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 328, 期 1-2, 页码 217-224出版社
SPRINGER
DOI: 10.1007/s11010-009-0092-7
关键词
Insulin resistance; Diabetes; HBP; ER stress; UDP-GlcNAc; OGT; RNAi; JNK; Glucose uptake; Skeletal muscle
类别
资金
- DBT
- ICMR
- DST-FIST, Government of India
- CSIR
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.
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