Muscle protein synthesis in the streptozotocin-diabetic rat. A possible role for corticosterone in the insensitivity to insulin infusion in vivo

Abstract

The effect of insulin infusion in vivo on muscle protein synthesis was investigated in rats. In 10-days-streptozotocin-diabetic rats infused in vivo with amino acids and glucose, the rate of protein synthesis per unit of RNA (RNA activity) was markedly decreased. Pre-treatment with large doses of insulin at 17 and 1 h before the infusion fully restored RNA activity to normal. Infusion of insulin for 6 h with amino acids and glucose did not restore RNA activity to normal in the diabetic rats. However, in diabetic-adrenalectomized rats similar infusions of insulin fully restored RNA activity to normal. Measurements of plasma corticosterone concentrations indicated a 50% increase in the diabetic rats. Since pre-treatment with corticosterone suppressed the stimulatory effect of insulin infusion on RNA activity in adrenalectomized rats, and since corticosterone treatment for 6 days suppressed RNA activity even though insulin concentrations were elevated, it is suggested that increased concentrations of corticosterone are responsible for the lag in response to insulin in the diabetic rat. This means that the catabolic effects of glucocorticoids must be also considered together with the catabolic effect of insulin lack in diabetes.

Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man.

“…Interestingly, muscles from insulin-deficient diabetic animals, which exhibit depressed rates of protein synthesis in vitro, do respond to insulin during the initial period of perfusion (4,7). In keeping with these observations, in vivo studies have readily shown an impairment in muscle protein synthesis in diabetic animals, which is at least partially reversible with insulin (27)(28)(29)(30), while stimulation of synthesis by insulin in nondiabetic animals has proved far more difficult to demonstrate (28). These considerations, coupled with the present study results, raise the possibility that the stimulatory effect of insulin on protein synthesis may be manifest in vivo at normal postabsorptive insulin concentrations.…”

Hormonal control of protein deposition in animals

“…There is evidence that this elevated corticosterone concentration inhibits the effects of exogenously applied insulin on muscle protein synthesis (Odedra & Millward, 1982;Odedra et al 1982). This is another example of a possible interrelationship between hormones, although in this case it would be more interesting if the relationship could be demonstrated in 'normal' animals.…”

“…Presumably this insulin is 'attempting' to counteract the catabolic effects of the glucocorticoids (Odedra & Millward, 1982). In diabetic rats, administration of insulin does not stimulate protein synthesis in muscle unless the animal is adrenalectomized; diabetic rats have higher corticosterone concentrations than controls (Odedra et al 1982). It is also interesting to note that while insulin promotes the uptake of amino acids into muscle, cortisol promotes an increased efflux of amino acids from muscle (Rannels & Jefferson, 1980;Lewis & Goldspink, 1982).…”

“…One of the most interesting findings from the type of studies outlined above, using adrenalectomized and intact animals given relatively large doses of glucocorticoids, is the interrelationships between plasma corticosterone and insulin concentrations. Presumably this insulin is 'attempting' to counteract the catabolic effects of the glucocorticoids (Odedra & Millward, 1982). In diabetic rats, administration of insulin does not stimulate protein synthesis in muscle unless the animal is adrenalectomized; diabetic rats have higher corticosterone concentrations than controls (Odedra et al 1982).…”

Insulin action on skeletal muscle protein metabolism during catabolic states

“…The glucocorticoidinduced hyperinsulinemia could not overcome this insulin resistance [60]. The [85].…”