Elevated insulin concentrations may influence cancer and cardiometabolic disease onset and prognosis, and lower insulin levels after exercise may contribute to disease prevention and overall health. The effect of exercise training on systemic and tissue-specific insulin supply and demand in breast cancer survivors and adults at risk for cardiometabolic disease is unclear. The objective of this dissertation was to evaluate the effects of exercise training on postmeal insulin concentrations in breast cancer survivors, and identify mechanisms responsible for changes to insulin supply and demand following exercise training in breast cancer survivors and adults at risk for cardiometabolic disease. Study 1 investigated differences between systemic and tissue-specific responses to exercise training and/or the anti-diabetes drug metformin in adults with prediabetes. Fasting proinsulin concentrations were lower following combined exercise and metformin (-24%), and insulin clearance was higher in the metformin and combined exercise and metformin groups (+19% and +17%). There were no differences in the exercise or placebo group, and taken together with previous work from our lab, suggests that exercise regulates insulin supply and demand systemically, while pharmacological adaptations may be tissue-specific. Study 2 evaluated the effects of physical activity on postmeal insulin concentrations in breast cancer survivors. Fifteen women completed 12 weeks of exercise training with pre- and post-intervention oral glucose tolerance testing. Insulin concentrations 120 minutes following glucose ingestion decreased (68.8±34.5 vs. 56.2±31.9 uU/ml, p Study 3 assessed the specific components of insulin supply and demand that may contribute to the blunted or absent postmeal insulin response observed in study 2. There was a significant increase in estimated skeletal muscle glucose uptake following exercise training (5.7±1.8 vs. 7.2 ±1.8, mmo*pmol*kg/m2 p