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Evaluation of markers for skeletal muscle atrophy and calcineurin/NFAT signaling in acute and chronic diabetes mellitis
Author(s) -
Roberts Tiffany Karla,
Donaldson Sue K,
Roberts Brian,
Gooch Jennifer L,
Price S Russ
Publication year - 2009
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.23.1_supplement.782.1
Subject(s) - nfat , endocrinology , medicine , atrophy , calcineurin , muscle atrophy , soleus muscle , skeletal muscle , muscle hypertrophy , streptozotocin , chemistry , diabetes mellitus , biology , transplantation
Diabetes mellitus (DM) causes persistent skeletal muscle atrophy. In a streptozotocin (STZ)‐induced rat model of DM, atrophy occured both acutely (3 d) and chronically (3 wk) and was greater in the mixed MHC fiber gastrocnemius (GAST) muscle than the predominantly MHCI fiber soleus muscle. In chronic STZ‐DM atrophy, switching of muscle fibers from Type MHCI to MHCII was also observed in the soleus. In this study, we have examined several markers of muscle atrophy including atrogin‐1 (AT‐1) and PGC1α mRNAs in GAST muscle of acute and chronic STZ‐DM rats and their controls. Since calcineurin activity is necessary to maintain MHCI fiber type, we also tested the hypothesis that calcineurin (Cn)/NFAT signaling would be decreased during atrophy by measuring CnA catalytic subunit protein and the mRNA of MCIP1.4, a NFAT‐regulated gene. In acute STZ‐DM rats AT‐1 was increased and PGC1α mRNA was decreased relative to Control muscle. CnA protein content was unchanged, and MCIP1.4 mRNA was decreased. In chronic STZ‐DM rats, AT‐1 mRNA was unchanged, whereas CnA protein and both MCIP1.4 and PGC1α mRNAs were decreased. These[PC1] findings indicate that STZ‐DM rapidly initiates and sustains muscle atrophy in the GAST. The decrease in Cn/NFAT signaling is also consistent with an atrophy process that occurs preferentially in MHC II fibers. Supported by NIH DK63658.