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Diabetologia
Published in: Diabetologia 3/2013

01-03-2013 | Article

Endoplasmic reticulum stress upregulates protein tyrosine phosphatase 1B and impairs glucose uptake in cultured myotubes

Authors: E. Panzhinskiy, Y. Hua, B. Culver, J. Ren, S. Nair

Published in: Diabetologia | Issue 3/2013

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Abstract

Aims/hypothesis

Endoplasmic reticulum (ER) stress has been recognised as a common pathway in the development of obesity-associated insulin resistance. Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signalling and is localised on the ER membrane. The aim of the study was to investigate the cross-talk between ER stress and PTP1B.

Methods

Leptin-deficient obese (ob/ob), Ptp1b (also known as Ptpn1) knockout and C57BL/6J mice were subjected to a high-fat or normal-chow diet for 20 weeks. ER stress was induced in cultured myotubes by treatment with tunicamycin. Immunohistochemistry and western blotting were used to assess proteins involved in the ER stress response. Myotube glucose uptake was determined by measuring 2-deoxy[3H]glucose incorporation.

Results

A high-fat diet induced ER stress and PTP1B expression in the muscle tissue of mice and these responses were attenuated by treatment with the ER chaperone tauroursodeoxycholic acid (TUDCA). Cultured myotubes exhibited increased levels of PTP1B in response to tunicamycin treatment. Silencing of Ptp1b with small interfering RNA (siRNA) or overexpression of Ptp1b with adenovirus construct failed to alter the levels of ER stress. Ptp1b knockout mice did not differ from the wild-type mice in the extent of tunicamycin-induced upregulation of glucose-regulated protein-78. However, tunicamycin-induced phosphorylation of eukaryotic initiation factor 2α and c-Jun NH2-terminal kinase-2 were significantly attenuated in the Ptp1b knockout mice. Treatment with TUDCA or silencing of PTP1B reversed tunicamycin-induced blunted myotube glucose uptake.

Conclusions/interpretation

Our data suggest that PTP1B is activated by ER stress and is required for full-range activation of ER stress pathways in mediating insulin resistance in the skeletal muscle.
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Metadata
Title
Endoplasmic reticulum stress upregulates protein tyrosine phosphatase 1B and impairs glucose uptake in cultured myotubes
Authors
E. Panzhinskiy
Y. Hua
B. Culver
J. Ren
S. Nair
Publication date
01-03-2013
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 3/2013
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2782-z

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