Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 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.
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PMID:Stimulation of lipolysis in humans by physiological hypercortisolemia. 193 85

Several neuropsychiatric illnesses, including depression and Alzheimer's disease, are reported to be characterized by hypercortisolemia and by reduced levels of cerebrospinal fluid somatostatin-like immunoreactivity (CSF-SLI). To investigate a possible causal linkage between these abnormalities we administered prednisone, 80 mg orally per day for 5 days, to 9 healthy volunteers. We observed significant prednisone-induced reductions in CSF-SLI. Moreover, the magnitude of these reductions was inversely related to the magnitude of prednisone-induced reductions in plasma ACTH levels, suggesting a functional interaction between circulating corticosteroids, central somatostatin and pituitary ACTH release.
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PMID:Prednisone decreases CSF somatostatin in healthy humans: implications for neuropsychiatric illness. 288 25

Hydrocortisone was infused overnight into nine normal healthy adults on three occasions at 0, 80, and 200 micrograms.kg-1.h-1, producing plasma cortisol concentrations of 10.6 +/- 1.2, 34.0 +/- 2.0, and 64.9 +/- 4.3 micrograms/dl, respectively. L-[1-13C]leucine, L-[phenyl-2H5]phenylalanine, and L-[2-15N]glutamine were infused during the last 7 h of hypercortisolemia to measure amino acid kinetics. During the last 3.5 h, somatostatin, glucagon, and insulin were infused to reduce the cortisol-induced elevation in plasma insulin to basal. Hypercortisolemia increased plasma glucose, free fatty acid (FFA), and insulin concentrations. Institution of the somatostatin clamp returned insulin to basal but increased glucose and FFA. Acute hypercortisolemia increased protein breakdown 5-20%, as measured by increases in leucine and phenylalanine appearance rates. Normalizing insulin during hypercortisolemia did not alter phenylalanine flux but enhanced leucine appearance rate, the latter result indicating that insulin was affecting leucine metabolism during hypercortisolemia. The fraction of the leucine flux that was oxidized was not significantly increased with hypercortisolemia, but disposal by the nonoxidative route of leucine uptake for protein synthesis was increased. Hypercortisolemia increased cycling of amino acids by increasing protein breakdown and synthesis, but the increase in this process could have increased resting energy expenditure (REE) only 1-2%. Hypercortisolemia increased glutamine flux in a dose-dependent fashion through an increase in de novo synthesis, which presumably reflects increased release from skeletal muscle. Hypercortisolemia increased REE 9-15% at the 80 and 200 micrograms.kg-1.h-1 infusion rates. Respiratory quotient did not rise with cortisol infusion but tended to decrease, suggesting that the increase in REE was fueled by increased oxidation of fat. These data demonstrate that hypercortisolemia increases metabolic rate and may be in part responsible for the hypermetabolic state in injury.
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PMID:Effect of cortisol on energy expenditure and amino acid metabolism in humans. 790 Jul 96

The present study was undertaken to determine whether an acute physiologic rise in plasma cortisol during selective insulin deficiency would have significant effects on glycerol and beta-hydroxybutyrate metabolism in conscious overnight-fasted dogs. Each experiment consisted of a two hour dye equilibration period, a 40 minute basal period, and a 3 hour experimental period. A continuous infusion of indocyanine green dye for blood flow estimation was initiated at the start of the equilibration period and continued throughout the experiment. In both of two protocols selective insulin deficiency was created during the experimental period by infusing somatostatin peripherally (0.8 microgram/kg-min) with basal replacement of glucagon intraportally (0.65 ng/kg-min). In the test protocol (CORTISOL, n = 5), 3.0 micrograms/kg-min of hydrocortisone was infused during the experimental period. In the control protocol (SALINE, n = 5), saline was infused. Net hepatic balances were determined using the (A-V) difference technique. During selective insulin deficiency alone (SALINE), the arterial blood glycerol level increased from 81 +/- 19 to 140 +/- 11 microM (p < 0.01) and net hepatic glycerol uptake (NHGlyU) tended to increase from 2.3 +/- 0.3 to 3.3 +/- 0.6 mumol/kg-min (0.05 < 0.1). The arterial plasma free fatty acid (FFA) level remained unchanged at 1041 +/- 35 microM. The arterial beta-hydroxybutyrate (BHOB) level increased slightly from 21 +/- 4 to 29 +/- 5 microM while net hepatic beta-hydroxybutyrate production (NHBP) remained unchanged (1.0 +/- 0.2 mumol/kg-min). During acute hypercortisolemia with selective insulin deficiency (CORTISOL), similar changes occurred in the arterial blood glycerol level and net hepatic glycerol uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of acute hypercortisolemia on beta-hydroxybutyrate and glycerol metabolism during insulin deficiency. 790 56

This study was undertaken to further investigate the effect of acute selective insulin deficiency on glycogenolysis and gluconeogenesis occurring during chronic physiological hypercortisolemia in conscious overnight fasted dogs. After an 80-min tracer and dye equilibration period and a 40-min basal period, selective insulin deficiency was created during the 180-min experimental period by infusing somatostatin peripherally (0.8 micrograms.kg-1.min-1) with basal replacement of glucagon intraportally (0.65 ng.kg-1.min-1). In the cortisol group (n = 5), a continuous infusion of hydrocortisone (3.5 micrograms.kg-1.min-1) was begun 5 days before the experiment. In the saline group (n = 5), there was no infusion of cortisol. [3-3H]glucose, [U-14C]alanine, and indocyanine green dye were used to assess glucose production and gluconeogenesis using tracer and arteriovenous difference techniques. During selective insulin deficiency in the saline group, the arterial plasma glucose level (Glc) increased from 109 +/- 2 to 285 +/- 19 mg/dl; glucose production increased from 2.7 +/- 0.2 to 4.5 +/- 0.3 mg.kg-1.min-1. Gluconeogenic efficiency and conversion of alanine to glucose (Conv) increased by 300 +/- 55 and 356 +/- 67%. During selective insulin deficiency in the cortisol group, Glc increased from 117 +/- 3 to 373 +/- 50 mg/dl; glucose production increased from 3.3 +/- 0.5 to 6.9 +/- 0.7 mg.kg-1.min-1. Gluconeogenic efficiency and Conv increased by 268 +/- 41 and 393 +/- 75%, respectively. The maximal glycogenolytic rate increased significantly more in the cortisol group than in the saline group, accounting for the difference in glucose production. These results suggest that, even during chronic hypercortisolemia, acute insulin deficiency has more pronounced effects on glycogenolysis than gluconeogenesis.
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PMID:Effects of chronic hypercortisolemia on carbohydrate metabolism during insulin deficiency. 817 83

For the purpose of obtaining an integral picture of anterior pituitary function in canine pituitary-dependent hyperadrenocorticism (PDH), 47 dogs with PDH and eight control dogs received combined administration of four hypophysiotropic hormones (CRH, GHRH, GnRH and TRH) and measurements were made of ACTH, cortisol, GH, LH, PRL and TSH. Basal plasma levels in 47 dogs with PDH were higher for ACTH, cortisol and PRL, lower for GH, and not different for LH (n = 25 noncastrated dogs) and TSH compared with controls (n = 8). In dogs with PDH the responses to combined hypophysiotropic stimulation, measured as increment and area under the curve (AUC), were not different for ACTH, lower for GH and TSH (increments and AUC) and higher for cortisol (increments), LH (AUC, n = 25 noncastrated dogs) and PRL (increments and AUC) than in controls. We conclude that pituitary function is altered in several respects in dogs with PDH. 1) In spite of persisting hypercortisolemia and the neoplastic transformation of the corticotropic cells, these cells usually remain responsive to combined hypophysiotropic stimulation. 2) Basal plasma GH concentrations and GH responsiveness in the combined stimulation test are decreased, probably as a result of the glucocorticoid-induced increase in somatostatin tone. 3) Plasma PRL concentrations and the PRL response to stimulation are increased, probably as a result of cosecretion with ACTH by the transformed corticotropic cells. 4) Despite the well known effect of glucocorticoids of decreasing circulating concentrations of gonadal steroids and thyroxine, the basal plasma concentrations of LH and TSH remain unchanged and there is a tendency to hyperresponsiveness to stimulation for LH and hyporesponsiveness for TSH. The most likely explanation for these changes is a dual effect of glucocorticoids: a direct effect on the gonads and thyroids and/or the transport and metabolism of their secretory products, and an influence on the sensitivity of the feedback control at the hypothalamic-pituitary level.
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PMID:Alterations in anterior pituitary function of dogs with pituitary-dependent hyperadrenocorticism. 937 28

Growth hormone (GH) deficiency occurs in about 30% of fibromyalgia patients. Treatment of GH deficient fibromyalgia patients with recombinant growth hormone improves several clinical features, including the tender point count. Defective GH secretion in these patients appears to be due to increased somatostatin tone in the hypothalamus. An hypothesis is presented which relates dysfunctional GH secretion to the effects of intermittent hypercortisolemia on upregulating the density of beta-adrenergic receptors in the hypothalamus. The resulting augmentation of beta-adrenergic tone stimulates the release of somatostatin, thus, impairing GH secretion.
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PMID:Disordered growth hormone secretion in fibromyalgia: a review of recent findings and a hypothesized etiology. 1002 88

Cortisol's effects on lipid metabolism are controversial and may involve stimulation of both lipolysis and lipogenesis. This study was undertaken to define the role of physiological hypercortisolemia on systemic and regional lipolysis in humans. We investigated seven healthy young male volunteers after an overnight fast on two occasions by means of microdialysis and palmitate turnover in a placebo-controlled manner with a pancreatic pituitary clamp involving inhibition with somatostatin and substitution of growth hormone, glucagon, and insulin at basal levels. Hydrocortisone infusion increased circulating concentrations of cortisol (888 +/- 12 vs. 245 +/- 7 nmol/l). Interstitial glycerol concentrations rose in parallel in abdominal (327 +/- 35 vs. 156 +/- 30 micromol/l; P = 0.05) and femoral (178 +/- 28 vs. 91 +/- 22 micromol/l; P = 0.02) adipose tissue. Systemic [(3)H]palmitate turnover increased (165 +/- 17 vs. 92 +/- 24 micromol/min; P = 0.01). Levels of insulin, glucagon, and growth hormone were comparable. In conclusion, the present study unmistakably shows that cortisol in physiological concentrations is a potent stimulus of lipolysis and that this effect prevails equally in both femoral and abdominal adipose tissue.
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PMID:Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans. 1206 58

Excess cortisol has been demonstrated to impair hepatic and extrahepatic insulin action. To determine whether glucose effectiveness and, in terms of endogenous glucose release (EGR), gluconeogenesis, also are altered by hypercortisolemia, eight healthy subjects were studied after overnight infusion with hydrocortisone or saline. Glucose effectiveness was assessed by a combined somatostatin and insulin infusion protocol to maintain insulin concentration at basal level in the presence of prandial glucose infusions. Despite elevated insulin concentrations (P < 0.05), hypercortisolemia resulted in higher glucose (P < 0.05) and free fatty acid concentrations (P < 0.05). Furthermore, basal insulin concentrations were higher during hydrocortisone than during saline infusion (P < 0.01), indicating the presence of steroid-induced insulin resistance. Postabsorptive glucose production (P = 0.64) and the fractional contribution of gluconeogenesis to EGR (P = 0.33) did not differ on the two study days. During the prandial glucose infusion, the integrated glycemic response above baseline was higher in the presence of hydrocortisone than during saline infusion (P < 0.05), implying a decrease in net glucose effectiveness (4.42 +/- 0.52 vs. 6.65 +/- 0.83 ml.kg-1.min-1; P < 0.05). To determine whether this defect is attributable to an impaired ability of glucose to suppress glucose production, to stimulate its own uptake, or both, glucose turnover and "hot" (labeled) indexes of glucose effectiveness (GE) were calculated. Hepatic GE was lower during cortisol than during saline infusion (2.39 +/- 0.24 vs. 3.82 +/- 0.51 ml.kg-1.min-1; P < 0.05), indicating a defect in the ability of glucose to restrain its own production. In addition, in the presence of excess cortisol, glucose disappearance was inappropriate for the prevailing glucose concentration, implying a decrease in glucose clearance (P < 0.05). The decrease in glucose clearance was confirmed by the higher increment in [3-3H]glucose during hydrocortisone than during saline infusion (P < 0.05), despite the administration of identical tracer infusion rates. In conclusion, short-term hypercortisolemia in healthy individuals with normal beta-cell function decreases insulin action but does not alter rates of EGR and gluconeogenesis. In addition, cortisol impairs the ability of glucose to suppress its own production, which due to accumulation of glucose in the glucose space results in impaired peripheral glucose clearance. These results suggest that cortisol excess impairs glucose tolerance by decreasing both insulin action and glucose effectiveness.
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PMID:Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects. 1296 73

Cushing's syndrome (CS) due to ectopic ACTH secretion (EAS) has a high morbidity and mortality, because of the underlying tumor and the sequelae of severe hypercortisolemia. Therefore, rapid treatment of ectopic CS is mandatory. Scintigraphy shows that up to 80% of ectopic ACTH-producing tumors have somatostatin receptors. While this suggests that somatostatin analogs may reduce ACTH production and treat patients with EAS, the therapeutic role of these agents is still evolving. Here we demonstrate the spectrum of responses to octreotide therapy in 3 patients with EAS. Diagnostic imaging with the 111In-pentetreotide scan did not predict the therapeutic response to octreotide. Two patients with positive somatostatin receptor scintigraphy failed to respond to octreotide, while one with a negative scan reached eucortisolemia on a maintenance dose of 75 microg octreotide twice daily or octreotide LAR 30 mg per month. We conclude that octreotide is not a first line agent to control hypercortisolemia but may be a useful agent when other inhibitors of steroidogenesis fail or parenteral administration is required. Before therapy an octreotide challenge test may predict therapeutic response. Cortisol levels should be monitored regularly on somatostatin analog therapy, because of its unpredictable long-term pharmacodynamic profile.
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PMID:Is there a therapeutic role for octreotide in patients with ectopic Cushing's syndrome? 1466 23


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