Beneficial effects of physical exercise for beta-cell maintenance in a type 1 diabetes mellitus animal model

Author(s)

Pimentel Villaca, Catharina de Barros ^[1] ; de Paula, Carolina Cavalcante ^[1] ; de Oliveira, Caroline Cruz ^[1] ; Vilas-Boas, Eloisa Aparecida ^[2] ; dos Santos-Silva, Junia Carolina ^[3] ; de Oliveira, Sergio Ferreira ^[1] ; Abdulkader, Fernando ; Ferreira, Sandra Mara ^{[4, 2]} ; Ortis, Fernanda ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci ICB, Dept Cell & Dev Biol, Ave Prof Lineu Prestes 1524, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci ICB, Dept Physiol & Biophys, Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Fac Med Sci, Dept Pharmacol, Campinas - Brazil

^[4] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas - Brazil

• Document type: Journal article
• Source: Experimental Physiology; v. 106, n. 7, p. 1482-1497, JUL 2021.
• Web of Science Citations: 0

Abstract

Physical exercise has beneficial effects on pancreatic beta-cell function and survival in a pro-inflammatory environment. Although these effects have been linked to decreased islet inflammation and modulation of pro-apoptotic pathways, little is known about the islet microenvironment. Our aim was to evaluate the effects of physical exercise in islet histomorphology in a mouse model of type 1 diabetes mellitus induced by multiple low doses of streptozotocin. As expected, induction of type 1 diabetes mellitus led to beta-cell loss and, consequently, decreased islet area. Interestingly, although the decrease in islet area was not prevented by physical exercise, this was not the case for the decrease in beta-cell mass. This was probably related to induction of beta-cell regeneration, because we observed increased proliferation and regeneration markers, such as Ki67 and Pcna, in islets of trained mice. These were found in the central and peripheral regions of the islets. An increase in the percentage of alpha- and delta-cells in these conditions, combined with an increase in proliferation and Pax4 labelling in peripheral regions, suggest that beta-cell regeneration might also occur by transdifferentiation. This agrees with the presence of cells double stained for insulin and glucagon only in islets of diabetic trained mice. In addition, this group had more extra-islet insulin-positive cells and islets associated with ducts than diabetic mice. Physical exercise also decreased nuclear factor-kappa B activation in islet cells of diabetic trained compared with diabetic untrained mice, indicating a decrease in pro-inflammatory cytokine-induced beta-cell death. Taken together, these findings indicate that preservation of beta-cell mass induced by physical exercise involves an increase in beta-cell replication and decrease in beta-cell death, together with islet neogenesis and islet cell transdifferentiation. (AU)

• FAPESP's process: 14/50867-3 - INCT 2014: National Institute of Science and Technology in Bioanalysis
• Grantee: Marco Aurelio Zezzi Arruda
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/04580-2 - Study of pancreatic beta cell demise: role of NF-kB, HNF4a and IL6 in the Diabetes mellitus development
• Grantee: Fernanda Ortis
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/26062-9 - Evaluation of the transcriptional factor HNF4± in beta cell function, viability and differentiation state, in conditions that can lead to development of Diabetes Mellitus
• Grantee: Fernanda Ortis
• Support Opportunities: Regular Research Grants