Influences of Corticosteroids on Cardiac Glycogen Concentration in the Rat

Abstract

Bilateral adrenalectomy resulted in a decrease (4.97 to 2.79 mg/g) in cardiac glycogen concentration in pentobarbital-anesthetized rats. Similar differences were observed at 10 to 14 days and at 27 days after adrenalectomy. Sham-adrenalectomized rats had normal cardiac glycogen concentration (4.98 mg/g). Total phosphorylase and phosphorylase a activities and glucose-6-phosphate concentrations in hearts obtained from adrenalectomized rats were not significantly different from controls. Total glycogen transferase activity was decreased in adrenalectomized rats and for any given glycogen concentration, the percent of the glycogen transferase in the independent form (percent transf erase I) was significantly lower in the adrenalectomized rats than in the intact controls. The glucocorticoid dexamethasone (40 /ig/day) prevented the decreases in cardiac glycogen concentration and percent transferase I in adrenalectomized rats. In the intact rat dexamethasone (40 /ig/day) increased cardiac glycogen concentration and total transferase activity to above control levels as did larger doses in both adrenalectomized and control rats. The mineralocorticoid deoxycorticosterone acetate (DOCA), had relatively little effect on cardiac glycogen concentration. Conclusion: glucocorticoids exert a regulatory role in cardiac glycogen metabolism. ADDITIONAL KEY WORDSglycogen transferase glycogen synthetase glycogen phosphorylase adrenalectomy glucocorticoids mineralocorticoids deoxycorticosterone acetate (DOCA) dexamethasone myocardial glycogen heart glycogen glucose-6-phosphate• In 1956, Russell and Bloom (1) reported that adrenalectomy does not alter the cardiac glycogen concentration in rats. However, Barta and Pavlovicova (2) recently demonstrated that cardiac glycogen is decreased in adrenalectomized rats. Furthermore, Suzuki (3) has shown that adrenalectomy markedly reduced the size and number of glycogen granules in myocardial cells in rats. In view of these recent developments, we undertook the present investigation with the following objectives: (1) to resolve this controversy, (2) to ascertain whether changes in the ac- This investigation was supported in part by U. S. Public Health Service Grants HE 06031 and HE 09924 from the National Heart Institute.Accepted for publication March 4, 1968.tivities of two major enzymes of glycogen metabolism, glycogen transferase (synthetase) and glycogen phosphorylase, are involved in the metabolic mechanism responsible for any changes in cardiac glycogen concentration consequent to adrenalectomy or corticosteroid treatment, and (3) to determine whether the corticosteroids exert a regulatory function in cardiac glycogen metabolism.Methods Animals,-Male, albino, Sprague-Dawley rats (210 to 350 g) were used. Rats were anesthetized with ether and bilaterally adrenalectomized via a dorsal lumbar approach. Rats with sham operations were similarly prepared except that the adrenals were not removed. The drinking water of all adrenalectomized-rats was 0.9% NaCl. All rats were fed Purina rat ...

Protective Role of Increased Myocardial Glycogen Stores in Cardiac Anoxia in the Rat

“…The lowering of cardiac glycogen in the presence of excess thyroid hormone (12, 13) may partially explain the relative intolerance of patients with angina pectoris to thyroid extract. Cardiac glycogen may also be lowered in adrenocortical insufficiency (15) and elevated in diabetes (11), hypothyroidism (14), hyperadrenalism (15), and physical training (13,17). Whether such changes in cardiac glycogen are of clinical significance is unknown.…”

“…Glycogen levels in the heart have a diurnal variation (10) and are affected by a variety of hormonal (11)(12)(13)(14)(15), dietary (16) and exercise factors (13,17), and by the prevention of catecholamine-induced glycogenolysis (18)(19)(20)(21). These changes in glycogen stores might be accompanied by altered mechanical responses to oxygen deprivation.…”

A Role for Sphingolipids in Producing the Common Features of Type 2 Diabetes, Metabolic Syndrome X, and Cushing’s Syndrome

“…When the compensatory increase in insulin levels was prevented, the effects on insulin receptor levels or binding affinity were abolished (106). Further downstream, corticosteroids have been shown to blunt the phosphorylation of Akt/PKB, 4E-BP1, p70S6K, and glycogen synthase (97,98,100,(107)(108)(109) and to inhibit the translocation and expression of GLUT4 (14,15). Elucidating the mechanisms underlying these antagonistic actions of glucocorticoids is not only important for comprehending the pathogenesis of Cushing's syndrome, but is also extremely relevant for understanding the complications associated with exogenous glucocorticoid therapy.…”

Protection against cardiac anoxia — role and limitations of increased glycogen reserves in the isolated rat right ventricular strip

“…This increase, however, only occurs in the presence of intact adrenal glands (12) -the glucocorticoids seem to play a "permissive" role, which can be partly explained by their effect of inducing the formation of cardiac glycogen synthetase (2).…”