glycogen and Cushing-Syndrome

The contribution of liver glycogen catabolism to hyperglycemia and glucose intolerance induced by pharmacological hypercortisolism were investigated.. For this purpose, adult male Wistar rats that received 1.0 mg/kg dexamethasone (DEX) ip at 8:00 a.m. (DEX group) or saline (CON group) once a day for 5 consecutive days were compared.. Experimental hypercortisolism was confirmed by higher (p<0.05) glycemia, lower (p<0.05) body weight and glucose intolerance. In the fed state, the basal glycogen catabolism and the glucagon (1 nM) and epinephrine (2 μM) induced glycogen catabolism were similar between the groups. The activation of glycogen catabolism induced by phenylephrine (2 μM) and isoproterenol (20 μM) were increased (p<0.05) and decreased (p<0.05), respectively, in DEX rats. Furthermore, DEX rats exhibited higher (p<0.05) glycogen catabolism during the infusion of cAMP (3 μM). However, during the infusion of cAMP (15 μM), 6MB-cAMP (3 μM) or cyanide (0.5 mM), the intensification of glycogen breakdown was similar. Thus, in general, hypercortisolism does not influence the basal glycogen catabolism and the liver responsiveness to glycogenolytic agents in the fed state. In contrast with fed state, fasted rats (DEX group) showed a more intense (p<0.05) basal glycogen catabolism.. The contribution of glycogen catabolism to hyperglycemia during hypercortisolism depends of the nutritional status, starting from a negligible participation in the fed state up to a significant contribution in the fasted state.

Topics: Animals; Body Weight; Cushing Syndrome; Cyclic AMP; Dexamethasone; Epinephrine; Fasting; Glucagon; Glucose Intolerance; Glycogen; Hyperglycemia; Liver; Male; Rats; Rats, Wistar

The neuroendocrine-specific protein 7B2, which serves as a molecular escort for proPC2 in the secretory pathway, promotes the production of enzymatically active PC2 and may have non-PC2 related endocrine roles. Mice null for 7B2 exhibit a lethal phenotype with a complex Cushing's-like pathology, which develops from intermediate lobe ACTH hypersecretion as a consequences of interruption of PC2-mediated peptide processing as well as undefined consequences of the loss of 7B2. In this study we investigated the endocrine and metabolic alterations of 7B2 null mice from pathological and biochemical points of view. Our results show that 7B2 nulls exhibit a multisystem disorder that includes severe pathoanatomical and histopathologic alterations of vital organs, including the heart and spleen but most notably the liver, in which massive steatosis and necrosis are observed. Metabolic derangements in glucose metabolism result in glycogen and fat deposition in liver under conditions of chronic hypoglycemia. Liver failure is also likely to contribute to abnormalities in blood coagulation and blood chemistry, such as lactic acidosis. A hypoglycemic crisis coupled with respiratory distress and intensive internal thrombosis most likely results in rapid deterioration and death of the 7B2 null.

Topics: Adrenocorticotropic Hormone; Animals; Blood Glucose; Cause of Death; Corticosterone; Cushing Syndrome; Glucagon; Glucose; Glycogen; Hormones; Hypothermia; Lactic Acid; Liver; Magnesium; Metyrapone; Mice; Mice, Knockout; Multiple Organ Failure; Nerve Tissue Proteins; Neuroendocrine Secretory Protein 7B2; Pituitary Hormones; Radioimmunoassay; Seizures; Tissue Distribution

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

Femoral and abdominal adipose tissue cellularity and metabolism as well as muscle morphology and metabolism were examined in women with Cushing's syndrome and compared with those in nonobese women and obese women with the android and gynoid types of fat distribution. Cushing's syndrome was characterized by abdominal obesity and enlarged abdominal fat cells, with adipose tissue lipoprotein lipase activity elevated 2-3 times that in normal women and low lipolytic capacity. Muscle tissue in women with Cushing's syndrome had a relatively low proportion of type I (30%) and a high proportion of type IIB (32%) muscle fibers, similar to those in android obesity (45% and 25%, respectively) and in contrast to fiber composition in gynoid obesity (55% and 12%, respectively). Glycogen synthase activity in the lateral vastus muscle was very low. We suggest that the enlargement of abdominal fat depots in women with Cushing's syndrome is at least partially due to elevated adipocyte lipoprotein lipase activity and low lipolytic activity. Furthermore, the abnormal muscle fiber composition might be caused by the corticosteroid excess. Such muscle is known to be relatively insulin insensitive and might thus contribute to the marked insulin resistance that occurs during chronic corticosteroid excess.

Topics: Adipose Tissue; Adolescent; Adult; Anthropometry; Cushing Syndrome; Female; Glycerol; Glycogen; Glycogen Synthase; Humans; Insulin; Lipolysis; Lipoprotein Lipase; Middle Aged; Muscles; Norepinephrine; Obesity

Topics: Acid Phosphatase; Alkaline Phosphatase; Cushing Syndrome; Eosinophils; Glycogen; Histocytochemistry; Humans; Hydrocortisone; Leukocyte Count; Leukocytes; Lymphocytes; Microscopy, Electron; Monocytes; Neutrophils; Peroxidases; RNA; Spectrophotometry; Staining and Labeling

Topics: Adult; Cushing Syndrome; Female; Glycogen; Histocytochemistry; Humans; Leukocytes; Male

Topics: Addison Disease; Age Factors; Bone Development; Calcium; Cartilage; Child; Cushing Syndrome; Enzyme Induction; Female; Glucocorticoids; Glycogen; Growth; Growth Hormone; Humans; Intestinal Absorption; Intrinsic Factor; Male; Sex Factors; Time Factors; Vitamin D