Beneficial effects of physical exercise for ß-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 hyperglycaemia owing to pancreatic ß-cell destruction by the immune system. Physical exercise has been shown to have potentially beneficial protective roles against cytokine-induced pancreatic ß-cell death, but its benefits are yet to be proved and should be understood better, especially in the islet environment. What is the main finding and its importance? Physical exercise protects against ß-cell loss in a well-described animal model for T1D, induced by multiple low doses of streptozotocin. This seems to be related to reduced cytokine-induced ß-cell death and increased islet cell proliferation. Contributions of islet neogenesis and/or transdifferentiation of pancreatic non-ß-cells into ß-cells cannot be excluded. ABSTRACT: Physical exercise has beneficial effects on pancreatic ß-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 ß-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 ß-cell mass. This was probably related to induction of ß-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 α- and δ-cells in these conditions, combined with an increase in proliferation and Pax4 labelling in peripheral regions, suggest that ß-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 ß-cell death. Taken together, these findings indicate that preservation of ß-cell mass induced by physical exercise involves an increase in ß-cell replication and decrease in ß-cell death, together with islet neogenesis and islet cell transdifferentiation.

Protein malnutrition blunts the increment of taurine transporter expression by a high-fat diet and impairs taurine reestablishment of insulin secretion.

Taurine (Tau) restores ß-cell function in obesity; however, its action is lost in malnourished obese rodents. Here, we investigated the mechanisms involved in the lack of effects of Tau in this model. C57BL/6 mice were fed a control diet (CD) (14% protein) or a protein-restricted diet (RD) (6% protein) for 6 wk. Afterward, mice received a high-fat diet (HFD) for 8 wk [CD + HFD (CH) and RD + HFD (RH)] with or without 5% Tau supplementation after weaning on their drinking water [CH + Tau (CHT) and RH + Tau (RHT)]. The HFD increased insulin secretion through mitochondrial metabolism in CH and RH. Tau prevented all those alterations in CHT only. The expression of the taurine transporter (Tau-T), as well as Tau content in pancreatic islets, was increased in CH but had no effect on RH. Protein malnutrition programs ß cells and impairs Tau-induced restoration of mitochondrial metabolism and biogenesis. This may be associated with modulation of the expression of Tau-T in pancreatic islets, which may be responsible for the absence of effect of Tau in protein-malnourished obese mice.-Branco, R. C. S., Camargo, R. L., Batista, T. M., Vettorazzi, J. F., Borck, P. C., dos Santos-Silva, J. C. R., Boschero, A. C., Zoppi, C. C., Carneiro, E. M. Protein malnutrition blunts the increment of taurine transporter expression by a high-fat diet and impairs taurine reestablishment of insulin secretion.