title: Expression of basic fibroblast growth factor, protein kinase C and members of the apoptotic pathway in skeletal muscle of streptozotocin-induced diabetic rats.
abstract: This study investigated the potential mechanisms that may underlie diabetes induced amyoatrophy. Sprague-Dawley rats were either injected intraperiotneally with STZ (test group; N=8) to induce diabetic-like symptoms (blood glucose level ≥16.65mmol/L) or with buffer (control group; N=8). Differences in muscle structure between the STZ-induced diabetic and control groups were evaluated by histochemistry. Protein and mRNA levels of basic FGF (bFGF), bax, bcl-2, and caspase 3 in skeletal muscle were compared between the 2 groups using immunohistochemistry and quantitative PCR, respectively. Serum level of insulin and protein kinase C (PKC) were measured by competitive RIA and ELISA, respectively. Unlike control animals, the skeletal muscle fibers from STZ-induced diabetic animals were broken and pyknotic, the sarcomeric structure disrupted, and mild hyperplasia of interstitial adipose tissues was detected. The serum level of PKC was higher (P=0.003) and the protein and mRNA levels of bFGF in skeletal muscle were lower (P=0.001) in STZ-induced diabetic versus control animals. Protein and mRNA levels of the apoptosis promoting genes caspase-3 and bax were higher in skeletal muscle from STZ-induced diabetic rats as compared to control animals (P<0.001 and P=0.037, respectively), while mRNA and protein levels of bcl-2, an inhibitor of apoptosis, was lower in STZ-induced diabetic rats versus control animals (P=0.026). Increasing apoptosis in skeletal muscle from STZ-induced diabetic rats was further demonstrated by TNNEL assay. Our findings suggest that enhanced PKC levels, reduction of bFGF expression, and increased in apoptosis might be associated with the development of diabetes-induced myoatrophy.
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: zhaoyuwu2005@126.com.
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Jingjiong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001284:Atrophy; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: D007328:Insulin; D016222:Fibroblast Growth Factor 2; D013311:Streptozocin; D011493:Protein Kinase C
keywords: Bax; Bcl-2; Caspase-3; Hyperglycemia; Muscle atrophy; Protein kinase C; bFGF