Insulin treatment reverses the increase in atrogin-1 expression in atrophied skeletal muscles of diabetic rats with acute joint inflammation

Autor(es)

Pinheiro-Dardis, Clara Maria ^[1] ; Gutierres, Vania Ortega ^[1] ; Assis, Renata Pires ^[1] ; Peviani, Sabrina Messa ^[2] ; Delfino, Gabriel Borges ^[2] ; Quagliotti Durigan, Joao Luiz ^[3] ; Salvini, Tania de Fatima ^[2] ; Baviera, Amanda Martins ^[1] ; Brunetti, Iguatemy Lourenco ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Clin Anal, Araraquara, SP - Brazil

^[2] Fed Univ Sao Carlos UFSCar, Dept Phys Therapy, Sao Carlos, SP - Brazil

^[3] Univ Brasilia, Phys Therapy Div, Brasilia, DF - Brazil

• Tipo de documento: Artigo Científico
• Fonte: THERAPEUTICS AND CLINICAL RISK MANAGEMENT; v. 14, p. 275-286, 2018.
• Citações Web of Science: 1

Resumo

Background: The aim of this study was to evaluate the changes in biomarkers of skeletal muscle proteolysis (atrogin-1, muscle RING finger-1 protein {[}MuRF-1]) and inflammation (nuclear factor kappa-B) in skeletal muscles of rats under two catabolic conditions, diabetes mellitus (DM) and acute joint inflammation, and the effects of insulin therapy. Materials and methods: Male Wistar rats were divided into groups without diabetes - normal (N), saline (NS), or iota-carrageenan (NCa) injection into the tibiotarsal joint - and groups with diabetes - diabetes (D), plus insulin (DI), saline (DS), or iota-carrageenan (DCa) injection into the tibiotarsal joint, or iota-carrageenan injection and treatment with insulin (DCaI). Three days after iota-carrageenan injection (17 days after diabetes induction), tibialis anterior (TA) and soleus (SO) skeletal muscles were used for analysis. Results: DM alone caused a significant decrease in the mass of TA and SO muscles, even with low levels of atrogenes (atrogin-1, MuRF-1), which could be interpreted as an adaptive mechanism to spare muscle proteins under this catabolic condition. The loss of muscle mass was exacerbated when iota-carrageenan was administered in the joints of diabetic rats, in association with increased expression of atrogin-1, MuRF-1, and nuclear factor kappa-B. Treatment with insulin prevented the increase in atrogin-1 (TA, SO) and the loss of muscle mass (SO) in diabetic-carrageenan rats; in comparison with TA, SO muscle was more responsive to the anabolic actions of insulin. Conclusion: Acute joint inflammation overcame the adaptive mechanism in diabetic rats to prevent excessive loss of muscle mass, worsening the catabolic state. The treatment of diabetic-carrageenan rats with insulin prevented the loss of skeletal muscle mass mainly via atrogin-1 inhibition. Under the condition of DM and inflammation, muscles with the prevalence of slow-twitch, type 1 fibers were more responsive to insulin treatment, recovering the ability to grow. (AU)

• Processo FAPESP: 10/00892-0 - Efeito da inflamação aguda do tornozelo sobre as características histológicas, a expressão gênica e níveis da creatina cinase e enzimas antioxidantes nos músculos sóleo e tibial anterior de ratos diabéticos
• Beneficiário: Iguatemy Lourenço Brunetti
• Modalidade de apoio: Auxílio à Pesquisa - Regular