Leptin Improves Insulin Sensitivity of Skeletal Muscle in Obese‐diabetic ob/ob Mice

The adipocyte hormone leptin, a potential treatment for obesity, increases glucose uptake by skeletal muscle of normal rodents, mediated mainly via the central nervous system. This study investigates whether leptin affects glucose uptake by skeletal muscle of insulin resistant obese-diabetic ob/ob mice which do not produce functional leptin. Uptake of 2-deoxyglucose by isolated soleus muscles of ob/ob mice was unaltered by incubation with leptin (10−9M), with or without insulin (10−6M). Administration of leptin (10μg, twice daily, i.p.) for 7 days approximately normalized food intake, plasma glucose and insulin concentration, and increased insulin-stimulated 2-deoxyglucose uptake by isolated soleus muscles. Similar effects resulted from pair-feeding, although the pair-feeding did not lower plasma insulin or body weight as much as leptin. The results suggest that leptin replacement in ob/ob mice reduces insulin resistance in skeletal muscle, and this effect is largely attributable to reduced food intake.