glycogen and Adrenocortical-Hyperfunction

Glucocorticoids include steroid hormones released from the adrenal cortex or synthetic analogues developed for various inflammatory and immune disorders. GCs are known to play an important role in maintaining the body's metabolic balance, but their irregular activity has been associated with complications like Cushing's syndrome, insulin resistance, and heart disease. Conventional GC action is through their nuclear receptor activation, but specific and non-specific membrane bound receptor mediated non-genomic actions have also been reported. GCs increase AMPK phosphorylation at Thr172, in addition to augmenting AMPK protein and gene expressions. AMPK is insulin mimetic in many of its actions like glucose uptake and inhibition of lipolysis, and these properties of AMPK are made used in conditions like insulin resistance and diabetes. Nevertheless, if AMPK is activated by GC in the absence of diabetes or decreased insulin signaling, accumulation of substrates in the form of glycogen and triglycerides could precipitate cardiac abnormalities. Glycogen storage can lead to many disorders like hypertrophy, conduction system disease and Wolff Parkinson White syndrome. TG accumulation is associated with generation of free radicals, ceramide formation, mitochondrial dysfunction and cardiac cell death. In this review, we outline the cardiometabolic changes associated with GC, especially related to augmentation in AMPK, and link these changes to cardiac dysfunction.

Topics: Adrenal Cortex; Adrenocortical Hyperfunction; AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Cardiomyopathies; Enzyme Activation; Glucocorticoids; Glucose; Glycogen; Heart; Humans; Lipid Metabolism; Myocardium; Triglycerides; Up-Regulation

Topics: Adipose Tissue; Adrenocortical Hyperfunction; Diabetes Mellitus; Glucocorticoids; Gluconeogenesis; Glycogen; Glycolysis; Humans; Insulin Resistance; Liver; Muscles

The effects of hypercorticism on the regulation of glycogen metabolism by insulin in skeletal muscles was examined by using the hindlimb perfusion technique. Rats were injected daily with either saline or dexamethasone (0.4 mg.kg-1.day-1) for 14 days and were studied in the fed or fasted (24 h) state under saline or insulin (1 mU/ml) treatment. In fed controls, insulin resulted in glycogen synthase activation and in enhanced glycogen synthesis. In dexamethasone-treated animals, basal muscle glycogen concentration remained normal, but glycogen synthase activity ratio was decreased in white and red gastrocnemius and plantaris muscles. Furthermore, insulin failed to activate glycogen synthase and glycogen synthesis. In the controls, fasting was associated with decreased glycogen concentrations and with increased glycogen synthase activity ratio in all four groups of muscles (P less than 0.01). Dexamethasone treatment, however, completely abolished the decrease in muscle glycogen content as well as the augmented glycogen synthase activity ratio associated with fasting. Insulin infusion stimulated glycogen synthesis in fasted controls but not in dexamethasone-treated rats. These data therefore indicate that dexamethasone treatment inhibits the stimulatory effect of insulin on glycogen synthase activity and on glycogen synthesis. Furthermore, hypercorticism suppresses the decrease in muscle glycogen content associated with fasting.

Topics: Adrenocortical Hyperfunction; Animals; Dexamethasone; Glucose; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Hormones; Insulin; Male; Muscles; Phosphorylases; Rats; Rats, Inbred Strains

The effect of hypercorticism on the regulation of glycogen metabolism by epinephrine was examined in skeletal muscles using a hindlimb perfusion technique. Rats were injected with either saline or dexamethasone (0.4 mg.kg-1.day-1) for 14 days and were studied in the fed and fasted (24 h) states under saline or epinephrine (10(-7) M) treatment. In the fed state, dexamethasone administration did not affect basal glycogen concentration but decreased glycogen synthase activity ratio in white and red gastrocnemius muscles. Epinephrine failed to decrease glycogen content despite the expected activation of glycogen phosphorylase in the fed dexamethasone-treated rats. Dexamethasone treatment resulted in a threefold increase in the level of muscle adenosine, a phosphorylase a inhibitor. In control rats, fasting was associated with a decrease in muscle glycogen concentration (P less than 0.01) and with an increase in the glycogen synthase activity ratio. Dexamethasone treatment, however, totally abolished both the decreased muscle glycogen content and glycogen synthase activation observed in fasting controls. In the dexamethasone-treated group, fasting restored the glycogenolytic effect of epinephrine. Interestingly, it was associated with decreased muscle adenosine concentrations. These data indicate that, in the fed state, dexamethasone treatment inhibits skeletal muscle glycogenolysis in response to epinephrine despite phosphorylase activation and glycogen synthase inactivation. It is suggested that this abnormality could be due to the inhibition of phosphorylase a by increased muscle adenosine levels.

Topics: Adenosine; Adrenocortical Hyperfunction; Animals; Epinephrine; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Glycogen Synthase; Lactates; Lactic Acid; Male; Nucleotides; Osmolar Concentration; Phosphorylase a; Phosphorylases; Rats; Rats, Inbred Strains

Topics: Adrenocortical Hyperfunction; Animals; Cushing Syndrome; Glucocorticoids; Gluconeogenesis; Glucose; Glycogen; Humans; Insulin; Insulin Resistance; Insulin Secretion; Liver; Receptor, Insulin

The effect of hypoxia, exercise, and thermal stress on myocardial metabolism have been widely investigated, but little attention has been paid to studying the effects of a combination of these stress. The influence of hypoxia as modified by physical exertion (swimming) and cold stress was therefore studied. The parameters investigated included myocardial glycogen and noradrenaline, serum free fatty acid, adrenal ascorbic acid, and adrenal weight. It was observed that maximal stress was produced when hypoxia was combined with physical exertion. No suppression of cold-induced lipolysis by hypoxia was observed, in contrast to previously reported observations. Maximal depletion of cardiac blycogen and cardiac noradrenaline was noted in hypoxic exercise. Adrenal overactivity was not found to be related to any particular stress but was seen to be proportional to the severity of the stress applied.

Topics: Adrenal Glands; Adrenocortical Hyperfunction; Animals; Ascorbic Acid; Cold Temperature; Fatty Acids, Nonesterified; Glycogen; Hypoxia; Lipid Metabolism; Male; Myocardium; Norepinephrine; Organ Size; Physical Exertion; Rats; Stress, Physiological

Topics: Adrenocortical Hyperfunction; Cortisone; Female; Glycogen; Liver; Pregnancy