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Diabetologia. 2012 Jan;55(1):204-14. doi: 10.1007/s00125-011-2328-9. Epub 2011 Oct 18.

Endoplasmic reticulum stress does not mediate palmitate-induced insulin resistance in mouse and human muscle cells.

Author information

1
Inserm, UMR-S 872, Centre de Recherche des Cordeliers, Paris 75006, France.

Abstract

AIMS/HYPOTHESIS:

Recent experiments in liver and adipocyte cell lines indicate that palmitate can induce endoplasmic reticulum (ER) stress. Since it has been shown that ER stress can interfere with insulin signalling, our hypothesis was that the deleterious action of palmitate on the insulin signalling pathway in muscle cells could also involve ER stress.

METHODS:

We used C2C12 and human myotubes that were treated either with palmitate or tunicamycin. Total lysates and RNA were prepared for western blotting or quantitative RT-PCR respectively. Glycogen synthesis was assessed by [¹⁴C]glucose incorporation.

RESULTS:

Incubation of myotubes with palmitate or tunicamycin inhibited insulin-stimulated protein kinase B (PKB)/ v-akt murine thymoma viral oncogene homologue 1 (Akt). In parallel, an increase in ER stress markers was observed. Pre-incubation with chemical chaperones that reduce ER stress only prevented tunicamycin but not palmitate-induced insulin resistance. We hypothesised that ER stress activation levels induced by palmitate may not be high enough to induce insulin resistance, in contrast with tunicamycin-induced ER stress. Indeed, tunicamycin induced a robust activation of the inositol-requiring enzyme 1 (IRE-1)/c-JUN NH₂-terminal kinase (JNK) pathway, leading to serine phosphorylation of insulin receptor substrate 1 (IRS-1) and a decrease in IRS-1 tyrosine phosphorylation. In contrast, palmitate only induced a very weak activation of the IRE1/JNK pathway, with no IRS1 serine phosphorylation.

CONCLUSIONS/INTERPRETATION:

These data show that insulin resistance induced by palmitate is not related to ER stress in muscle cells.

PMID:
22006247
DOI:
10.1007/s00125-011-2328-9
[Indexed for MEDLINE]

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