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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of glucocorticoids on adipose tissue lipolysis in animals and humans is controversial. To determine whether a physiological increase in plasma cortisol, similar to that observed in diabetic ketoacidosis and other stress conditions, stimulates lipolysis, palmitate kinetics were measured in seven nondiabetic volunteers on two occasions with [1-14C]palmitate as a tracer. Subjects received a 6-h infusion of either 2 micrograms.kg-1.min-1 hydrocortisone or saline in random order. On both occasions, a pancreatic clamp (0.12 micrograms.kg-1.min-1 somatostatin, 0.05 mU.kg-1.min-1 insulin, and 3 ng.kg-1.min-1 growth hormone) was used to maintain plasma hormone concentrations at desired levels. Plasma cortisol concentrations increased to approximately 970 nM during cortisol infusion. Palmitate rate of appearance (Ra) and concentration increased by approximately 60% during cortisol infusion but did not change during saline infusion. Increments in palmitate Ra and concentration over the 6-h study were significantly greater during cortisol than saline infusion when compared by area-under-the-curve analysis (152 +/- 52 vs. -48 +/- 23 mumol.kg-1 and 12.2 +/- 4.1 vs. -4.9 +/- 4.1 mmol.min-1.L-1, respectively; P less than 0.02). Plasma glucose concentrations did not change significantly during cortisol (5.0 +/- 0.3 vs. 6.1 +/- 0.6 mM, NS) or saline (4.9 +/- 0.2 vs. 4.9 +/- 0.1 mM, NS) infusion. In nondiabetic volunteers, a 6-h cortisol infusion was associated with a 60% increase in palmitate Ra that did not occur with saline infusion. Thus, physiological hypercortisolemia may contribute to the increased rates of lipolysis observed in humans during stress.
Diabetes 1991 Oct
PMID:Stimulation of lipolysis in humans by physiological hypercortisolemia. 193 85

Branched-chain alpha-keto acid dehydrogenase (BCKAD) is a multisubunit complex regulated by phosphorylation and is considered to be rate-limiting for branched-chain amino acid (BCAA) metabolism in skeletal muscle. Glucocorticoids increase net protein degradation in muscle; associated with this increased breakdown of muscle protein is an elevated rate of BCAA oxidation. The effects of glucocorticoids on skeletal muscle BCKAD were investigated in different rat models. BCKAD was activated after glucocorticoid treatment (both acutely, within 2 h, and chronically). The amount of enzyme per muscle cell increased after 5 d of cortisone acetate treatment. Insulin administration partially blocked the acute effects of glucocorticoids on muscle BCKAD. Activation was also observed during metabolic acidosis, insulinopenic diabetes mellitus, and endotoxic shock, three conditions characterized by elevated circulating glucocorticoids, increased BCAA oxidation, and increased net protein breakdown. Activation of BCKAD may account for the increased oxidation of BCAA observed during hypercortisolemia. The sequelae of this accelerated catabolism may include increased glutamine and alanine production for gluconeogenesis and provision of ATP for muscle work.
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PMID:Glucocorticoid regulation of muscle branched-chain amino acid metabolism. 238 1

Activation of skeletal muscle insulin receptor tyrosine kinase in vitro and in vivo was studied in two rat models of insulin resistance: insulinopenic diabetes and hypercortisolemia. In control rats, intravenous insulin administration resulted in dose-dependent in vivo activation of the muscle insulin receptor kinase towards histone H2b. Half-maximal and maximal activation were observed 5 min after injecting 0.1 and 0.5 U insulin/100 g, respectively. Diabetes (7 days) induced with streptozotocin did not affect insulin binding affinity of solubilized muscle receptors but depressed receptor kinase activation in vivo by 52 or 40% after intravenous insulin administration (0.1 or 2 U/100 g, respectively). Cortisone treatment (5 days) resulting in weight loss, hyperglycemia, and hyperinsulinemia did not affect the number, insulin binding affinity, or kinase activity of solubilized receptors activated with insulin in vitro or in vivo. It is concluded that impaired insulin receptor tyrosine kinase activation was demonstrated in vivo in rats with insulinopenic diabetes and that glucocorticoid-induced insulin resistance probably reflects postreceptor defect(s) in muscle.
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PMID:Effects of hypercortisolemia and diabetes on skeletal muscle insulin receptor function in vitro and in vivo. 264 42

A diabetic cat with hyperadrenocorticism had polydipsia, polyuria, ventral abdominal alopecia, thin dry skin, and a pendulous abdomen. Results of laboratory testing indicated persistent resting hypercortisolemia, hyperresponsiveness of the adrenal glands (increased cortisol concentration) to ACTH gel, and no suppression of cortisol concentrations after administration of dexamethasone at 0.01 or 1.0 mg/kg of body weight. Necropsy revealed a pituitary gland tumor, bilateral adrenal hyperplasia, hepatic neoplasia, and demodicosis. Adrenal gland function was concurrently assessed in 2 cats with diabetes mellitus. One cat had resting hypercortisolemia, and both had hyperresponsiveness to ACTH gel (increased cortisol concentration) at one hour. After administration of dexamethasone (0.01 and 1.0 mg/kg), the diabetic cats appeared to have normal suppression of cortisol concentrations. The effects of mitotane were investigated in 4 clinically normal cats. Adrenocortical suppression of cortisol production occurred in 2 of 4 cats after dosages of 25, 37, and 50 mg/kg. Three cats remained clinically normal throughout the study. One cat experienced vomiting, diarrhea, and anorexia.
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PMID:Hyperadrenocorticism in a cat. 355 96

Diabetes mellitus was induced in Lewis rats by streptozotocin, and these animals and control rats fed ad lib were studied after 7 weeks. At the time of sacrifice, nondecalcified histological sections of bone were prepared and subsequently quantitated by micromorphometric techniques. In addition, tibial alkaline phosphatase and mineral ash content were determined. The bones obtained from the diabetic animals are characterized by significant decrements in the quantities of osteoid and osteoclasts and by failure to acquire a tetracycline label. These histological features are attended by reduced quantities of urinary hydroxyproline and tibial alkaline phosphatase. As compared with control animals fed ad lib, diabetic rats are hyperphosphatemic and markedly hypercalciuric. Circulating alkaline phosphatase is also elevated and associated with a parallel increase in intestinal content of this enzyme. Although serum corticosterone levels are increased, diabetes is associated with decrements in both circulating immunoreactive parathyroid hormone and 1,25(OH)2D. We conclude that prolonged streptozotocin-induced diabetes mellitus in the rat results in reduced bone turnover. The relative roles that functional caloric deprivation, low circulating levels of 1,25(OH)2D, hypercalciuria, hypercortisolemia, and decreased blood parathyroid hormone levels play in the genesis of these skeletal abnormalities remain to be determined.
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PMID:The effect of streptozotocin-induced chronic diabetes mellitus on bone and mineral homeostasis in the rat. 645 Feb 54

Diurnal concentrations of glucose, the major regulatory hormones, and selected biochemistries were measured serially throughout a 25-h period in 38 healthy type I diabetic patients, 25 patients with acute ketoacidosis, and 20 normal subjects. Poor glucose control, meal intolerance, and hypercortisolemia were the dominant abnormalities in the healthy diabetic subjects. Ketonemia due to elevated plasma beta-hydroxybutyrate concentrations without ketonuria (nitroprusside reaction) was a frequent finding in a group of poorly controlled diabetic subjects. In the patients with acute ketoacidosis, the dominant abnormalities were overproduction of epinephrine and cortisol. High glucagon and growth hormone concentrations were documented in about one-half of these patients. We conclude that (1) the hyperglycemia, meal intolerance, and abnormal ketone body metabolism seen in these patients are caused by inadequacies in their insulin regimens; (2) ketone body underutilization contributes to diabetic ketosis; (3) epinephrine and cortisol overproduction are important components of acute ketoacidosis; and (4) the complex hormone-metabolic interactions in type I diabetes can best be explained by a multihormonal hypothesis with the primary defect being loss of beta-cell function.
Diabetes Care
PMID:Hormone and metabolic profiles in children and adolescents with type I diabetes mellitus. 682 6

A 76-year-old diabetic woman with non-obese Cushing's syndrome developed poor glycemic control with glibenclamide. She presented with a slight weight loss while bedridden due to a fall. Cushing's syndrome in this patient was suspected because of hypercortisolemia with eosinopenia, and adrenal Cushing's syndrome was diagnosed by endocrine and radiological examinations. A right adrenal adenoma was confirmed by autopsy. In this patient, progressive obesity and other common features of Cushing's syndrome may have been concealed by aging itself and coexisting diabetes mellitus.
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PMID:Non-obese Cushing's syndrome in an aged woman with non-insulin-dependent diabetes mellitus. 877 70

Carbohydrate and lipid metabolism was cross-sectionally assessed in 16 patients with endogenous hypercortisolism (endogenous Cushing syndrome). Five patients (31%) had fasting glucose levels over 6.6 mmol/l and a HbA1C over 7.5%. Six patients (38%) had diabetes mellitus based on an abnormal 75 g oral glucose tolerance test (OGTT) and two additional patients (13%) had impaired glucose tolerance based on an OGTT. Compared to obese individuals, patients with Cushing syndrome had an elevated glucose but no elevated insulin response to the OGTT. Regression analysis showed positive correlations between 24-h urinary free cortisol (UFC) and fasting blood glucose (P < 0.0005), UFC and OGTT glucose area under the curve (AUC) (P < 0.01), and UFC and HbA1C (P < 0.005). UFC levels were negatively correlated (P < 0.05) with OGTT insulin AUC and insulin/glucose ratios. Eleven (69%) patients required anti-hypertensive therapy for blood pressure control. Total cholesterol and triglycerides were elevated in patients with Cushing syndrome compared to obese controls, while LDL and HDL cholesterol, and Lp(a) were similar in the two groups. We conclude that impaired glucose tolerance and/or diabetes in patients with endogenous Cushing syndrome is due to the hyperglycemic effects of cortisol with relative insulinopenia. Thus, Cushing syndrome shares features with both the Metabolic Syndrome X and NIDDM, including impaired glucose uptake, hyperlipidemia and hypertension. However, in Cushing syndrome, a relative insulinopenia occurs, while in Metabolic Syndrome X and NIDDM, insulin excess is observed. In Cushing syndrome, as the hypercortisolemia exacerbates, insulinopenia becomes more paramount, suggesting that cortisol exerts a direct or indirect "toxic" effect on the beta-cell.
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PMID:Carbohydrate and lipid metabolism in endogenous hypercortisolism: shared features with metabolic syndrome X and NIDDM. 907 4

We report a rare case of Cushing's syndrome due to bilateral adrenocortical adenomas in a 45-year-old female. She suffered from diabetes mellitus and hypertension for a decade, but her appearance was not Cushingoid. The plasma cortisol level in the morning was at the upper limit of the normal range, but did not show a diurnal rhythm or was suppressed by 1 mg of dexamethasone. The plasma level of ACTH was undetectable, and it failed to respond to human CRH (hCRH). Plasma cortisol responded well to synthetic ACTH. The urinary 17-OHCS level was high, and was not suppressed by 4 mg of dexamethasone. While these findings were consistent with a diagnosis of adrenocortical adenoma, computed tomography showed several nodules in both adrenal glands that suggested the presence of huge nodular adrenocortical hyperplasia or bilateral adrenocortical adenomas. Bilateral adrenalectomy demonstrated the presence of three adenomas, two in the right and one in the left adrenal. Analysis of the extract from each adenoma revealed that two of the three produced an excess amount of cortisol. Magnetic resonance imaging (MRI) of the brain suggested the presence of pituitary adenoma. Prior to adrenalectomy, TSH, GH or LH showed a low response to TRH, GHRH or LHRH, respectively. Since normal responses were restored after bilateral adrenalectomy, these abnormalities were attributed to hypercortisolemia.
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PMID:A rare case of Cushing's syndrome due to bilateral adrenocortical adenomas. 944 86

The aim of the present study was to examine corticosterone dynamics and its role in the pathogenesis of impaired wound healing in diabetes mellitus (DM). The streptozotocin-treated rat was used as an animal model for type I DM. A linear skin incision and subcutaneously implanted polyvinyl alcohol sponge disks were considered as wound-healing models. The data regarding corticosterone dynamics revealed diabetes-related increments in plasma corticosterone concentrations at various time intervals during the diurnal cycle (9:00 a.m., 12:00 noon, and 3:00 p.m.) Moreover, a reduction in the levels of hippocampal glucocorticoid receptors was also evident in this disease state. Immobilization-induced stress elevated plasma corticosterone levels in both control and 30-day diabetic rats. Although the diabetic rat seems capable of appropriately initiating a corticosterone stress response, it is dramatically impaired in its capacity to terminate it. A progressive decrease in collagen deposition on polyvinyl alcohol sponge and wounded skin tensile strength was seen as a function of the duration of diabetes. Similarly, polyvinyl alcohol sponges retrieved from 30-day diabetic rats also showed a marked reduction in the expression of mRNA transcripts for type I and type III collagen. A simulation of the impairment in wound-healing potential in DM was achieved by treating control animals with a supraphysiological dose of hydrocortisone. It is worthy of note that an endocrinological paradigm involving adrenalectomy and replacement therapy with hydrocortisone significantly improved the wound-related parameters, including collagen metabolism and wounded skin tensile strength in the streptozotocin diabetic rats. Overall, our data provide evidence that the diabetic state is associated with hypercortisolemia and that this phenomenon may contribute to impaired wound healing in DM.
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PMID:Glucocorticoid dynamics and impaired wound healing in diabetes mellitus. 946 81


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