Hypertrophy Skeletal muscle in STZ diabetic rats.

• Grant number: 16/15766-7
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2016
• End date: May 31, 2019
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Rui Curi
• Grantee: Rui Curi
• Host Institution: Centro de Ciências Biológicas e da Saúde. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil
• Associated researchers: Marco Aurélio Salomão Fortes
• Associated scholarship(s): 18/06594-3 - Morphometric analysis of soleus and EDL muscles in muscular hypertrophy in rats with type I Diabetes Mellitus, BP.TT

Abstract

The diabetic state undertakes the function of skeletal muscle myopathy and causes reduction in skeletal muscle mass. Strength training is prescribed as part of treatment of diabetes mellitus (DM) because it improves glycemic control and promote increased muscle mass. Recently, we observed that compensatory hypertrophy of the soleus and long digital extensor (EDL) due to functional overload after 30 days of streptozotocin-induced DM is similar to in control rats. However, the signaling pathways involved in the activation of protein synthesis were different between groups. Thus, it is unclear how the diabetic animals have a lower muscle mass, respond similarly to controls functional overload. In this study, we propose to evaluate the muscular hypertrophy induced functional overload and intracellular mechanisms involved, signaling the synthesis and degradation pathways of proteins, autophagy and endoplasmic reticulum stress, concomitant with the establishment of the diabetic state in rats. The experiments will be performed in the muscles with predominance of oxidative fibers (soleus) or glycolytic (EDL). They are evaluated changes in synthesis pathways and protein degradation (protein molecular markers: Akt, rpS6, AMPK and 4EBP-1 total and phosphorylated (p-Akt (Thr473), p-rpS6 (ser240 / 244), p-AMPK ( Thr172), p-4EBP-1 (Thr37 / 46), MuRF-1 and atrogin-1 and RNA: FAK (focal adhesion kinase), Wnt7a, axina2, myostatin, follistatin, IGF-1 (insulin-like growth factor ), MG53 (mitsugumin 53) and ²-catenin, autofágicas pathways (protein molecular markers: LC3 (light chain 3 protein), Beclin1, Atg7 (autophagy-related protein 7), p62 (p62 - SQSTM1 protein -Sequestosome 1) ULK1 (Unc-51-like kinase 1) and p-ULK1 and response to ill-folded protein (PDI (protein disulfide isomerase), BiP (binding immunoglobulin protein), CHOP (CCAAT / enhancer binding protein - C / EBP) homologous protein ) EiF2± (eukaryotic initiation factor 2±) and p-EiF2± and RNA: CHOP, BIP XBP1 (X-box binding protein 1), IRE1± (inositol Requiring enzyme 1 alpha), PERK (protein kinase R-like ER protein kinase) and ATF6 (activating transcription factor 6) seven days after induction of hypertrophy ablation of the tibial muscle and tenotomy of the gastrocnemius muscle. The objective is to determine signaling pathways involved in the synthesis and degradation of proteins, autophagy or endoplasmic reticulum stress that can maintain or reduce the loss of muscle mass in the diabetic state. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

M.M. ANTUNES; C.B. DE ALMEIDA-SOUZA; G. GODOY; A.R. CRISMA; L.N. MASI; R. CURI; R.B. BAZOTTE. Adipose tissue is less responsive to food restriction anti-inflammatory effects than liver, muscle, and brain in mice. Brazilian Journal of Medical and Biological Research, v. 52, n. 1, 2018-12-10. (16/15766-7)

TATAGIBA KUWABARA, WILSON MITSUO; FUKUSAWA YOKOTA, CAROLINE NAOMI; CURI, RUI; ALBA-LOUREIRO, TATIANA CAROLINA. Obesity and Type 2 Diabetes mellitus induce lipopolysaccharide tolerance in rat neutrophils. SCIENTIFIC REPORTS, v. 8, DEC 3 2018. (16/15766-7, 18/09868-7, 15/03175-1)

SCERVINO, MARIA V. M.; FORTES, MARCO A. S.; VITZEL, KAIO F.; DE SOUZA, DIEGO R.; MURATA, GILSON M.; SANTANA, GIOVANNA O.; DA SILVA, ELIANE B.; LEVADA-PIRES, ADRIANA C.; KUWABARA, WILSON M. T.; LOUREIRO, TATIANA C. A.; et al. Autophagy signaling in hypertrophied muscles of diabetic and control rats. FEBS OPEN BIO, v. 13, n. 9, p. 14-pg., 2023-07-26. (16/11661-6, 16/15766-7, 19/19097-0, 20/00707-0, 19/02175-9)