Resistance training improves pancreatic beta cell function and survival in healthy and diabetic rodents

Author(s)

Gabriela Alves Bronczek

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2023-03-24

Examining board members

Antonio Carlos Boschero; Claudio Chrysostomo Werneck; Sandra Lucinei Balbo; Maria Lúcia Bonfleur; Helena Cristina de Lima Barbosa

• Advisor: Antonio Carlos Boschero

Abstract

Resistance exercise exerts beneficial effects on glycemic control in healthy and diabetic conditions. Here we investigated if such an effect could be due to exercise-induced alterations in beta cell function and survival. For this, we used C57BL/6 mice in two groups: control (CON, sedentary) and resistance exercise training (RET, 10 weeks of training). We also used a rat pancreatic beta-cell line (INS-1E) incubated with medium containing 10% of serum from CON or RET mice for 24h; followed by exposure to CPA (25 µM), an endoplasmic reticulum (ER) stressor, for 16h; or the pro-inflammatory cytokines interleukin-1ß (10 U/ml) plus interferon-'y' (100 U/ml), for 24h. Next, we used C57BL/6 mice in two groups: control (CTL) and type 1 diabetes (MLDS, i.p. injection of 40 mg/kg of streptozotocin for 5 days). After confirmation of the diabetic state, mice were divided into two other groups: MLDS (sedentary), and MLDS+RET (resistance training for 10 weeks). Healthy trained mice (RET) displayed improved glucose tolerance and reduced glycemia, with no alterations in insulin sensitivity. RET mice presented higher insulinemia in a fed state, associated with increased insulin secretion. Islets from RET mice showed reduced expression of genes related to ER stress, associated with increased expression of Ins2. INS 1E cells incubated with trained serum displayed a pattern of insulin secretion and gene expression similar to isolated islets from trained mice. When exposed to CPA, trained serum preserved the secretory function of INS 1E cells, and prevented CPA-induced apoptosis. Moreover, the increased insulin secretion in INS-1E cells incubated with trained serum may be due to increased expression of GLUT2 and glucokinase. In cells exposed to cytokines, trained serum preserved both insulin secretion and glucokinase expression, reduced expression of proteins related to apoptotic pathways, and protected cells from cytokine-induced apoptosis. In MLDS mice, resistance training reduced glycemia (fasting and fed) and improved glucose tolerance, which may be explained by the increased insulinemia (fasting and fed) and beta cell mass observed in diabetic-trained mice. In conclusion, resistance training stimulates the release of humoral factors which can make beta cells more resistant to harmful conditions and improve their secretory response to a glucose stimulus (AU)

• FAPESP's process: 18/15032-9 - Effect of resistance exercise training upon pancreatic beta-cell mass and function in healthy and diabetic mice
• Grantee: Gabriela Alves Bronczek
• Support Opportunities: Scholarships in Brazil - Doctorate