Type 1 diabetes (T1D) is provoked by an autoimmune assault against pancreatic β cells. Exercise training enhances β‐cell mass in T1D. Here, we investigated how exercise signals β cells in T1D condition. For this, we used several approaches. Wild‐type and IL‐6 knockout (KO) C57BL/6 mice were exercised. Afterward, islets from control and trained mice were exposed to inflammatory cytokines (IL‐1β plus IFN‐γ). Islets from control mice and β‐cell lines (INS‐1E and MIN6) were incubated with serum from control or trained mice or medium obtained from 5‐aminoimidazole‐4 carboxamide 1‐β‐ d ‐ribofuranoside (AICAR)‐treated C2C12 skeletal muscle cells. Subsequently, islets and β cells were exposed to IL‐1β plus IFN‐γ. Proteins were assessed by immunoblotting, apoptosis was determined by DNA‐binding dye propidium iodide fluorescence, and NO* was estimated by nitrite. Exercise reduced 25, 75, and 50% of the IL‐1β plus IFN‐γ‐induced iNOS, nitrite, and cleaved caspase‐3 content, respectively, in pancreatic islets. Serum from trained mice and medium from AICAR‐treated C2C12 cells reduced β‐cell death, induced by IL‐1β plus IFN‐γ treatment, in 15 and 38%, respectively. This effect was lost in samples treated with IL‐6 inhibitor or with serum from exercised IL‐6 KO mice. In conclusion, muscle contraction signals β‐cell survival in T1D through IL‐6.—Paula, F.M.M., Leite, N. C., Vanzela, E. C., Kurauti, M. A., Freitas‐Dias, R., Carneiro, E. M., Boschero, A. C., Zoppi, C. C. Exercise increases pancreatic β‐cell viability in a model of type 1 diabetes through IL‐6 signaling. FASEB J. 29, 1805‐1816 (2015). www.fasebj.org

Background/Aims: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease’s (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amount and intensity of the training or possible effects of adaptation to exercise and produced conflicting results regarding the benefits of parental exercise to the next generation. We employed a precisely regulated exercise regimen to study the transgenerational inheritance of improved metabolic health. Methods: We subjected male mice to a well-controlled exercise -training program to investigate the effects of paternal exercise on glucose tolerance and insulin sensitivity in their adult progeny. To investigate the molecular mechanisms of epigenetic inheritance, we determined chromatin markers in the skeletal muscle of the offspring and the paternal sperm. Results: Offspring of trained male mice exhibited improved glucose homeostasis and insulin sensitivity. Paternal exercise modulated the DNA methylation profile of PI3Kca and the imprinted H19/Igf2 locus at specific differentially methylated regions (DMRs) in the skeletal muscle of the offspring, which affected their gene expression. Remarkably, a similar DNA methylation profile at the PI3Kca, H19, and Igf2 genes was present in the progenitor sperm indicating that exercise-induced epigenetic changes that occurred during germ cell development contributed to transgenerational transmission. Conclusion: Paternal exercise might be considered as a strategy that could promote metabolic health in the offspring as the benefits can be inherited transgenerationally.

According, to the World Health Organization (WHO), overweight and obesity represent a rapidly growing threat to worldwide health. Currently, more than 1.4 billion adults are overweight. Although genetic factors account for some cases of obesity, it is evident that a drastic change in lifestyle is a main cause that accounts for the worldwide obesity and type 2 diabetes (T2D) prevalence. Physical exercise prevents or attenuates main obesity outcomes such as fat accumulation, insulin resistance, dyslipidemia, hypertension, and glucose intolerance. Considering the relevance of cells and the benefits of exercise to the onset of T2D, in the present chapter, we review several studies that have evaluated the effects of exercise training on β-cell function and survival in health, obesity, and diabetes. Although the literature still lacks conclusive data in this field, exercise training that enhances β-cell survival is a common outcome in all of the studies. Exercise training-induced alterations on β-cell functions are more controversial. Generally, the studies indicate that in healthy and obese insulin-resistant subjects, exercise decreases nutrient-induced insulin secretion (associated with a correspondent increase in insulin action); however, increased insulin secretion occurs in T2D.