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Heat shock mediated JNK inactivation improves insulin signaling in skeletal muscle
Author(s) -
Gupte Anisha A,
Bomhoff Gregory L.,
Touchberry Chad D.,
Dollerschell John T.,
Geiger Paige C.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a836-c
Subject(s) - anisomycin , phosphorylation , hsp70 , insulin resistance , kinase , medicine , endocrinology , insulin receptor , heat shock protein , insulin , western blot , skeletal muscle , microbiology and biotechnology , biology , chemistry , biochemistry , gene
Insulin resistance is associated with increased phosphorylation of IRS‐1 at Ser307. One of the kinases thought to mediate the inhibitory serine phosphorylation of IRS‐1 is c‐Jun N‐terminal Kinase (JNK). Induction of heat shock protein 70 (HSP70) by heat shock treatment (HST) has been shown to inhibit JNK activation in cell culture through direct HSP70/JNK interaction. We hypothesize that induction of HSP70 will result in decreased JNK activation and improved insulin signaling in skeletal muscle. HSP70 protein expression was induced in isolated soleus muscles of Fisher 344 rats aged 2 mo (young) and 24 mo (old) by exposing the muscles to mild heat (42°C) for 60 minutes followed by a 12 h recovery period at 30°C. Following recovery, soleus muscles were incubated in the presence or absence of anisomycin (10μg/ml) for 30 min to induce JNK phosphorylation. Western blot analysis revealed an increase in HSP70 protein expression (~78% above basal) with HST and a decrease in anisomycin‐induced JNK phosphorylation in both young and old rats. Although the older rats had higher basal pSer307 IRS‐1 phosphorylation, HST effectively reduced Ser phosphorylation of IRS‐1 in both young and old rats. This suggests that HST improves sensitivity of IRS‐1 for insulin signaling with potential to reverse the effects of insulin resistance.