Mechanisms Responsible For Greater Insulin-Stimulated Glucose Transport After Exercise
Over 130 million Americans suffer from the devastating consequences of type 2 diabetes or prediabetes. Skeletal muscle accounts for up to 85% of insulin-induced blood glucose clearance, and insulin resistance for muscle glucose uptake is an essential defect for type 2 diabetes. One exercise bout can enhance subsequent insulin-stimulated glucose uptake (ISGU) by skeletal muscle, but the mechanisms have remained elusive. Using our Akt substrate of 160 kDa-knockout (AS160-KO) rats, we made the breakthrough discovery that muscle expression of AS160 (a key regulator of GLUT4 glucose transporter localization) is essential for elevated postexercise ISGU (PEX-ISGU) in both sexes. Studying male AS160-KO rats with AAV to deliver wildtype (WT) or phosphomutated AS160, we found that preventing AS160 phosphorylation (pAS160) on key sites that regulate GLUT4 translocation partially reduced (~45%), but did not eliminate PEX-ISGU. Using identical methods in female rats, we discovered that preventing pAS160 on the same sites did not lower PEX-ISGU. These results suggest that improved PEX-ISGU in male versus female rats does not rely on entirely identical mechanisms. This project aims to advance fundamental knowledge to identify the underlying mechanisms responsible for a major health benefit of exercise.