Beneficial effects of physical exercise for β-cell maintenance in a Type 1 Diabetes mellitus animal model.

NEW FINDINGS What is the central question of this study? Type 1 Diabetes mellitus (T1D) leads to hyperglycemia due a destruction of pancreatic β-cells by the immune system. Physical exercise has been shown to have potential beneficial protective roles against cytokine-induced pancreatic β-cell death, however its benefits are yet to be proven and should be better understood especially in the islet environment. What is the main finding and its importance? Physical exercise protects against β-cell loss in a well described animal model for T1D, induced by multiple-low-doses-streptozotocin. This seems to be related to: 1. Reduced cytokine-induced β-cell death and 2. Increased islet cell proliferation. Contribution of islet neogenesis and/or transdifferentiation of pancreatic non-β-cells into β-cells cannot be excluded. ABSTRACT Physical exercise has beneficial effects on pancreatic β-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 on the islet microenvironment. Our aim was to evaluate the effects of physical exercise in islet histomorphology in a T1D mouse model induced by multiple low doses of streptozotocin. As expected, induction of T1D leads to β-cell loss and consequently decreased islets area. Interestingly, although the decrease in islet area is not prevented by physical exercise, β-cell mass decrease is. This is probably related to induction of β-cell regeneration, since we observed increased proliferation and regeneration markers, such as Ki67 and PCNA, in islet of trained mice. These were found in the center and peripheral region of the islets. Increase in the percentage of α and δ-cells in this condition, together with increase in proliferation and PAX4 labeling in peripheral regions, suggest that β-cell regeneration may also occur by transdifferentiation. This agrees with 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 NFκB activation in islet cells of Diabetic Trained compared to Diabetic mice, indicating a decrease in pro-inflammatory cytokine-induced β-cell death. Altogether, these findings indicate that β-cell mass preservation induced by physical exercise involves increase in β-cell replication and decrease in β-cell death, together with islet neogenesis and islet cell transdifferentiation. This article is protected by copyright. All rights reserved.