EXERCISE FOR STUDYING TYPE 1 DIABETES IN A NON-OBESE DIABETIC (NOD) MOUSE MODEL

The incidence of Type 1 Diabetes Mellitus (T1DM) is markedly growing in the past two decades. For the management of this disease, physical exercise has been recommended as a costeffective treatment throughout the global health system. The Non-Obese Diabetic (NOD) mouse represents a well-established experimental model analogous to human T1DM as it is characterized by a progressive autoimmune destruction of pancreatic β-cells. This thesis explored the uses of a mouse motorized treadmill to study the effects of exercise in NOD mice. Body mass, blood glucose level, immunological soluble factors, muscular performance and islets of Langerhans architecture were monitored during 12-week moderate-intensity endurance training in female NOD mice. After 12 weeks of training, no differences were registered as to diabetes incidence (50 vs 45%) and mean glycemia between sedentary controls and mice on exercise (190±34 vs 163±38 mg/dl, mean and SD). Exercise capacity dimished in the exercisingmice with respect to controls (work, distance, VO2max, p<.05). Preliminary data from a morphometric analysis of pancreata indicated the presence of larger infiltrates along with increased endocrine cellareas in the NOD exercising-mice. A higher infiltrate-to-islet ratio was observed in exercising-micewith respect to the controls. An exercise-induced weight loss was also detected. Among key anti- and pro-inflammatory cytokines: TNF-α, MIP-1β and IL-10 resulted to be lower at end of the training in the exercising animals with respect to pre-training values (1353±2 vs 1355±2.3; 984.6±12 vs 1001±37; 396±8.1 vs 407±27 MFI, respectively,p<.05) whereas IL-2P40 was higher in exercising-mice compared baseline (543±12 vs 539±15 MFI, p<.05). Further studies are needed to clarify the utility of the NOD mouse model to mimic and investigate the exercise effects in T1DM, immunomodulation and inflammation. Specifically, dose-response studies in which exercise will be administered to NOD mice at various levels of intensity will be necessary to determine the optimal regimen of physical exercise having clearcut preventive effects on the development of T1DM.