Beneficial Effects Of Physical Exercise For Beta-Cell Maintenance In A Type 1 Diabetes Mellitus Animal Model

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.