Glucocorticoid effects on insulin- and IGF-I-regulated muscle protein metabolism during aging

Abstract

This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin-and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25·9 and 58·1% respectively. In old rats, this effect was even greater, being 49·3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoidinduced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.

Dexamethasone-mediated regulation of death and differentiation of muscle cells. Is hydrogen peroxide involved in the process?

“…The appearance of muscle cell senescence was found instead of fragmented chromatin in the pictures obtained from the electron microscope after 200 nM Dex treatment. This observation was in agreement with previous reports [13,25] indicating that glucocorticoids might play a less clear physiological role in a progressive loss of muscle mass and developing mental dementia during ageing. The exact mechanism of glucocorticoid-induced cell death is unknown, although several reports indicate transcriptional glucocorticoid-mediated collapse of antioxidant systems with consequent ROS generation and an increase in calcium influx and structural deterioration of the cell [5,8,9,25,26,38].…”

Effects of a vitamin D analog, alfacalcidol, on bone and skeletal muscle in glucocorticoid-treated rats

“…Glucocorticoids stimulate muscle proteolysis (10,22) and inhibit protein synthesis (10, 41), resulting in muscle atrophy and muscle dysfunction. Glucocorticoid-induced myopathy is characterized by a decrease in the size of muscle fibers (13).…”

Insulin action on skeletal muscle protein metabolism during catabolic states

“…The target of glucocorticoids was the ATP-ubiquitin proteasome system [18]. An increase in proteolysis was visible in both groups in the presence of insulin (although of minor importance in old rats) because the glucocorticoid treatment always blunted the antiproteolytic action of insulin [20].…”

“…Elevated proteolysis has already been claimed in skeletal muscle of diabetic rats [5,63]. It [20,38,71].…”