In this study, researchers investigated the relationship between skeletal muscle triglyceride (mTG) levels and insulin action in 38 nondiabetic male Pima Indians. They found that higher mTG levels were inversely related to insulin sensitivity, as measured by glucose disposal rates during euglycemic-hyperinsulinemic clamps. mTG was negatively correlated with insulin sensitivity at both physiological and supraphysiological insulin levels, as well as with nonoxidative glucose disposal. However, mTG was not related to measures of adiposity such as body fat percentage, BMI, or waist-to-thigh ratio. In multiple regression analyses, mTG was independently associated with insulin resistance measures, while measures of obesity were related to insulin resistance independent of mTG. The study suggests that skeletal muscle insulin sensitivity is influenced by local triglyceride levels, as well as by remote fat depots and circulating lipids. The findings support the idea that skeletal muscle triglyceride levels play a significant role in insulin action and may be a key factor in the development of insulin resistance. The study highlights the importance of skeletal muscle triglyceride content in insulin-mediated glucose disposal and suggests that further research is needed to understand the mechanisms underlying this relationship.In this study, researchers investigated the relationship between skeletal muscle triglyceride (mTG) levels and insulin action in 38 nondiabetic male Pima Indians. They found that higher mTG levels were inversely related to insulin sensitivity, as measured by glucose disposal rates during euglycemic-hyperinsulinemic clamps. mTG was negatively correlated with insulin sensitivity at both physiological and supraphysiological insulin levels, as well as with nonoxidative glucose disposal. However, mTG was not related to measures of adiposity such as body fat percentage, BMI, or waist-to-thigh ratio. In multiple regression analyses, mTG was independently associated with insulin resistance measures, while measures of obesity were related to insulin resistance independent of mTG. The study suggests that skeletal muscle insulin sensitivity is influenced by local triglyceride levels, as well as by remote fat depots and circulating lipids. The findings support the idea that skeletal muscle triglyceride levels play a significant role in insulin action and may be a key factor in the development of insulin resistance. The study highlights the importance of skeletal muscle triglyceride content in insulin-mediated glucose disposal and suggests that further research is needed to understand the mechanisms underlying this relationship.