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

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 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 βcell 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 β-cell mass. This was probably related to induction of β-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 αand δ-cells in these conditions, combined with an increase in proliferation and Pax4 labelling in peripheral regions, suggest that β-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-κB activation in islet cells of diabetic trained compared with diabetic untrained mice, indicating a decrease in pro-inflammatory cytokine-induced β-cell death. Taken together, these findings indicate that preservation of β-cell mass induced by physical exercise involves an increase in β-cell replication and decrease in β-cell death, together with islet neogenesis and islet cell transdifferentiation.

Impacts of an Exercise Intervention on the Health of Pancreatic Beta-Cells: A Review

“…Exercise training enhances the beta-cell mass of T1DM patients. Studies showed that 8-weeks of high-intensity (60 min/d, 5 times/week) treadmill running reduced inflammatory factors and apoptosis (15–38%) of pancreatic beta-cells through the IL-6 signaling pathway [ 20 ], a 6-week treadmill exercise program stimulated the beta-cells proliferation, inhibited cytokine-induced beta-cells death, and, finally, improved the beta-cell mass [ 23 ].…”

Physical Activity as a Modern Intervention in the Fight against Obesity-Related Inflammation in Type 2 Diabetes Mellitus and Gestational Diabetes

“…As mentioned above, β-cell apoptosis is also observed in human pancreatic sections and post-mortem islet grafts in hyperglycaemic conditions [ 108 ]. Exercise positively influences β-cells, preventing apoptosis or increasing proliferation in islets, which leads to better control of the number of β-cells in the diabetic pancreas and increases the number of small islets [ 109 , 110 ].…”