Insulin preserves fast-twitch muscle mass during early STZ-induced diabetes in rats

Skeletal muscle atrophy is a critical complication of type 1 diabetes mellitus (T1DM), primarily caused by insulin deficiency. While physical activity is known to improve metabolic health, its effectiveness in preventing diabetes-induced muscle atrophy, particularly in the absence of insulin, remains unclear. This study examined the effects of voluntary exercise on muscle atrophy in an early phase streptozotocin (STZ)-induced diabetic rat model.

STZ was administered to male Wistar rats and SPORTS rats, which maintain high activity levels even after diabetes onset. Blood glucose levels, skeletal muscle mass, and muscle atrophy-related gene expression (Atrogin-1 and MuRF1) were measured, as well as locomotor activity. The effects of insulin, the sodium-glucose cotransporter (SGLT) inhibitor phlorizin, and leucine supplementation were also examined.

Extensor digitorum longus (EDL) muscle mass decreased significantly within seven days of diabetes onset, accompanied by early expression of atrophy-related genes. Insulin administration prevented the decrease in EDL muscle mass, whereas phlorizin did not, despite improving hyperglycemia. SPORTS rats maintained high voluntary locomotor activity after diabetes onset but failed to prevent muscle atrophy. Metabolomic analysis indicated altered branched-chain amino acid (BCAA) metabolism in diabetic muscle tissue. Leucine supplementation partially attenuated muscle atrophy in STZ-treated diabetic rats.

These findings suggest that insulin deficiency, rather than decreased physical activity, is a major contributor to early muscle atrophy in this model. Voluntary exercise alone is insufficient to prevent STZ-induced muscle atrophy in the absence of insulin. Leucine supplementation may offer a potential therapeutic strategy for muscle preservation.