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)

We examined splanchnic metabolism of alanine in 15 normal males under three sets of conditions: infusion of saline (control studies); infusion of somatostatin (SRIF) (bihormonal deficiency of insulin and glucagon); and infusion of somatostatin plus insulin (selective glucagon deficiency). Net splanchnic alanine uptake (NSAU) remained stable over 2 h during infusion of saline. Infusion of SRIF was associated with a fall in estimated hepatic plasma flow (EHPF) whether or not insulin was infused concomitantly. With SRIF only, arterio-hepatic venous alanine differences increased such that NSAU remained stable over 2 h, despite the fall in EHPF. In contrast, with selective glucagon deficiency, NSAU fell significantly after 2 h, an effect consequent on a fall in EHPF and a delayed fall in arterio-hepatic venous (A-HV) alanine differences. Our studies are compatible with a role for basal glucagon in maintenance of splanchnic extraction of alanine in normal man. However, the SRIF-initiated fall in EHPF may exert an influence on A-HV alanine differences independent of changes in pancreatic hormone secretion.
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PMID:Splanchnic metabolism of alanine in intact man. Effects of somatostatin and somatostatin plus insulin. 43 78

To determine the relationship between decreases in glucose and metabolic regulation in the absence of counterregulatory hormones, we infused overnight-fasted, conscious, adrenalectomized dogs (lacking cortisol and EPI) with somatostatin (to eliminate glucagon and growth hormone) and intraportal insulin (30 pmol.kg-1.min-1), creating arterial insulin levels of approximately 2000 pM. Glucose was infused during one 120-min period, two 90-min periods, and one 45-min period to establish levels of 5.9 +/- 0.1, 3.4 +/- 0.1, 2.5 +/- 0.1, and 1.7 +/- 0.1 mM, respectively. NE levels were 1.24 +/- 0.23, 1.85 +/- 0.27, 2.04 +/- 0.26, and 2.50 +/- 0.20 nM, respectively. During the euglycemic control period, the liver took up glucose (7.5 +/- 1.9 mumol.kg-1.min-1), but hypoglycemia triggered successively greater rates of net hepatic glucose output (3.0 +/- 0.7, 4.6 +/- 0.9, and 6.9 +/- 1.4 mumol.kg-1.min-1). Total gluconeogenic precursor uptake by the liver increased with hypoglycemia. Intrahepatic gluconeogenic efficiency rose progressively (by 106 +/- 42, 199 +/- 56, and 268 +/- 55%). Both glycerol and NEFA levels rose, indicating lipolysis was enhanced. Net hepatic NEFA uptake and ketone production increased proportionally, but the ketone level rose only with severe hypoglycemia. In conclusion, despite marked hyperinsulinemia and the absence of glucagon, EPI, and cortisol, we observed that lipolysis and glucose and ketone production increase in response to decreases in glucose. This suggests that neural and/or autoregulatory mechanisms can play a role in combating hypoglycemia.
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PMID:Relationship between decrements in glucose level and metabolic response to hypoglycemia in absence of counterregulatory hormones in the conscious dog. 139 5

The effects of acute pH changes on whole body leucine kinetics (1-13C-leucine infusion technique) were determined in normal subjects. Plasma insulin, glucagon, and growth hormone concentrations were kept constant by somatostatin and replacement infusions of the three hormones. When acidosis was produced by ingestion of NH4Cl (4 mmol kg-1 p.os; n = 8) arterialized pH decreased within 3 h from 7.39 +/- 0.01 to 7.31 +/- 0.01 (P less than 0.001) and leucine plasma appearance increased by 0.13 +/- 0.04 mumol kg-1 min-1 (P less than 0.02); in contrast, when alkalosis was produced by intravenous infusion of 4 mmol kg-1 NaHCO3 (n = 7, pH 7.47 +/- 0.01), leucine plasma appearance decreased by -0.09 +/- 0.04 mumol kg-1 min-1 (P less than 0.01 vs. acidosis). Whole body leucine flux also increased during acidosis compared to alkalosis (P less than 0.05), suggesting an increase in whole body protein breakdown during acidosis. Apparent leucine oxidation increased during acidosis compared to alkalosis (P = 0.05). Net forearm leucine exchange remained unaffected by acute pH changes. Plasma FFA concentrations decreased during acidosis by -107 +/- 67 mumol l-1 (P less than 0.05) and plasma glucose increased by 1.90 +/- 0.25 mmol l-1 (P less than 0.02); in contrast, alkalosis resulted in an increase in plasma FFA by 83 +/- 40 mumol l-1 (P less than 0.02; P less than 0.01 vs. acidosis), suggesting an increase in lipolysis; plasma glucose decreased compared to acidosis (P less than 0.01). The data demonstrate that acute metabolic acidosis and alkalosis, as they occur in clinical conditions, influence protein breakdown, and in the opposite direction, lipolysis.
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PMID:Effect of acute acidosis and alkalosis on leucine kinetics in man. 154 Oct 83

Net hepatic glucose uptake (NHGU) is much greater during oral or intraportal glucose loading than during peripheral intravenous glucose delivery even when similar glucose loads and hormone levels reaching the liver are maintained. To determine whether this difference is influenced by the hepatic nerves, nine conscious 42-h-fasted dogs in which a surgical denervation of the liver (liver norepinephrine levels postdenervation averaged 2.4% of normal) had been performed were subjected to a 40-min control period and two randomized 90-min test periods during which somatostatin (0.8 microgram.kg-1.min-1), intraportal insulin (1.2 mU.kg-1.min-1), and intraportal glucagon (0.5 ng.kg-1.min-1) were infused. The glucose load to the liver was increased twofold by infusing glucose into a peripheral vein (Pe) or the portal vein (Po). Arterial insulin and glucagon concentrations were 39 +/- 2 and 39 +/- 3 microU/ml and 55 +/- 5 and 54 +/- 7 pg/ml during Pe and Po, respectively. The hepatic glucose loads were 50.3 +/- 4.4 and 51.4 +/- 5.8 mg.kg-1.min-1 while NHGU was 2.1 +/- 0.5 and 2.2 +/- 0.7 mg.kg-1.min-1 during Pe and Po, respectively. Similar hormone levels and glucose loads reaching the liver in dogs with intact hepatic nerve supplies were previously shown to be associated with NHGU of 1.4 +/- 0.7 and 3.5 +/- 0.8 mg.kg-1.min-1 in the presence of peripheral and portal glucose delivery, respectively. In conclusion, an intact nerve supply to the liver appears to be vital for the normal response of the liver to intraportal glucose delivery.
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PMID:Role of hepatic nerves in response of liver to intraportal glucose delivery in dogs. 159 Mar 77

Somatostatin is widely distributed within the nervous system and the gastrointestinal tract. Gastrointestinal actions of somatostatin include inhibition of hormone release, reduction of pancreatic secretion, inhibition of motility, and reduction of blood flow. The purpose of this study was to investigate the role of somatostatin and its analogue octreotide on water and electrolyte transport in the small intestine. Rabbit ileal segments (n = 17) were harvested and arterially perfused ex vivo with a nonrecirculating oxygenated sanguineous solution. The lumen was perfused with an isotonic solution containing carbon 14-labeled polyethylene glycol. Net fluxes of water, Na+, and Cl- were calculated for three 20-minute periods designated basal, drug infusion, and recovery. Three groups were studied: somatostatin at 10(-6) mol/L (n = 5), somatostatin at 10(-5) mol/L (n = 5), and octreotide at 10(-5) mol/L (n = 7). Somatostatin at 10(-5) mol/L yielded a proabsorptive effect on the flux of water and electrolytes. Octreotide at 10(-5) mol/L caused a significant (p less than 0.05) proabsorptive response in the fluxes of water, sodium, and chloride during the period of drug infusion, which returned to basal secretory levels during the recovery period. This proabsorptive effect occurred without alterations in vascular resistance and necessarily was independent of systemic hormone interaction, supporting a direct effect of octreotide on intestinal ionic transport.
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PMID:Direct proabsorptive effect of octreotide on ionic transport in the small intestine. 224 38

The role of elevated plasma epinephrine concentrations in the regulation of plasma leucine kinetics and the contribution of beta-receptors were assessed in man. Epinephrine (50 ng/kg per min) was infused either alone or combined with propranolol (beta-blockade) into groups of six subjects fasted overnight; leucine flux, oxidation, and net plasma leucine forearm balance were determined during 180 min. Constant plasma insulin and glucagon concentrations were maintained in all studies by infusing somatostatin combined with insulin and glucagon replacements. Plasma leucine concentrations decreased from baseline during epinephrine infusion by 27 +/- 5 mumol/liter (P less than 0.02) due to a 22 +/- 6% decrease in leucine flux (P less than 0.05 vs. controls receiving saline) and to an increase in the metabolic clearance rate of leucine (P less than 0.02). Leucine oxidation decreased by 36 +/- 8% (P less than 0.01 vs. controls). beta-Blockade abolished the effect of epinephrine on leucine flux and oxidation. Net forearm release of leucine increased during epinephrine (P less than 0.01), suggesting increased muscle proteolysis; the fall of total body leucine flux was therefore due to diminished proteolysis in nonmuscle tissues, such as splanchnic organs. Nonoxidative leucine disappearance as a parameter of protein synthesis was not significantly influenced by epinephrine. Plasma glucose and FFA concentrations increased via beta-adrenergic mechanisms (P less than 0.001). The results suggest that elevation of plasma epinephrine concentrations similar to those observed in severe stress results in redistribution of body proteins and exerts a whole body protein-sparing effect; this may counteract catabolic effects of other hormones during severe stress.
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PMID:Elevation of plasma epinephrine concentrations inhibits proteolysis and leucine oxidation in man via beta-adrenergic mechanisms. 256 73

The current studies were designed to evaluate the role of plasma insulin and glucose as regulators of intestinal glucose transport in vivo. Initially, rats received either intravenous glucose infusion or intraperitoneal streptozotocin to induce sustained hyperglycemic hyperinsulinemia or hyperglycemic hypoinsulinemia. Net jejunal uptake rates of glucose were measured in vivo at several perfusate concentrations, and the kinetic constants, corrected for diffusion barrier resistance, were derived. Maximal velocity (Jmax) was increased 1.8-fold by hyperglycemic hyperinsulinemia and 2.6-fold by hyperglycemic hypoinsulinemia compared with controls, whereas Km and passive permeability of glucose were unchanged. The rate of L-proline uptake at saturation conditions was not increased by these experimental interventions. The corrected kinetic constants for jejunal glucose transport in streptozotocin diabetic rats kept normoglycemic and normoinsulinemic with insulin were similar to controls. Finally, induction of normoglycemic hyperinsulinemia by intravenous glucose-insulin infusion increased Jmax 1.8-fold, similar to hyperglycemic hyperinsulinemia, but induction of hyperglycemic normoinsulinemia by intravenous glucose-somatostatin infusion did not change Jmax. In conclusion, changes in plasma insulin but not glucose concentration cause a specific and reversible increase in Jmax of intestinal glucose transport. Hypoinsulinemia is a more potent signal than hyperinsulinemia. The membrane level, microvillus or basolateral, at which insulin induces an increased number of glucose transporters in intestinal epithelial cells remains to be defined.
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PMID:Insulin modulates rat intestinal glucose transport: effect of hypoinsulinemia and hyperinsulinemia. 265 75

The effect of a long acting somatostatin analogue SMS 201-995 on stomal effluents in patients with severe short bowel syndrome was investigated in a double blind placebo controlled balance study. Six patients, five with Crohn's disease and one with radiation enteropathy were studied. Five patients had a jejunostomy and one an ileostomy. The patients had a normal food intake, but because of severe malabsorption had received home parenteral nutrition for several years. Faecal mass was reduced (p less than 0.005) and intestinal net sodium absorption was increased (p less than 0.005) by intravenous infusion of SMS 25 micrograms/h. Net absorption of potassium, calcium, magnesium phosphate, zinc, nitrogen and fat was not influenced. Subcutaneous injections of 50 micrograms SMS every 12 hours had a similar effect on net intestinal absorption of sodium and water. Four patients continued with a five to six months open follow up study when subcutaneous SMS in the same dose was administered by the patients at home. The effect on faecal sodium loss persisted, but in one patient faecal mass gradually increased and finally exceeded pretreatment values. SMS may decrease net absorption of water and sodium following reduced secretion of digestive juices rather than by increasing absorptive capacity. SMS may be useful as an antidiarrhoeal drug in patients with high output jejuno- or ileostomies, but in patients who need permanent parenteral nutrition the effect is too small to significantly alter management.
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PMID:Effect of a long acting somatostatin analogue SMS 201-995 on jejunostomy effluents in patients with severe short bowel syndrome. 231 26

Net flux of insulin, glucagon, somatotropin, somatomedin-C, and somatostatin across the portal-drained viscera and liver of four lactating Holstein cows was measured at 4 and 8 wk postpartum. Cows were fed ad libitum intake a 60:40 corn silage:concentrate diet and milked at 12-h intervals. Milk yield and DM intake were 32.2 and 15.6 kg/d respectively. Twenty-four consecutive measurements of insulin, glucagon, and somatotropin net flux were obtained at 30-min intervals; 12 hourly measurements were obtained for somatomedin-C and somatostatin. Net flux is venous-arterial concentration difference times blood flow. Net flux of somatomedin-C was not detectable across the portal-drained viscera or liver. Somatotropin was removed by total splanchnic tissues. There was net production of somatostatin across portal-drained viscera, but net flux of somatostatin across liver was not significant. On a net basis, removal of insulin and glucagon by liver accounted for 66% of portal-drained visceral production. Within cows and sampling days, increases in net portal-drained visceral production of insulin and glucagon often were mirrored by increases in net removal by liver. As in other species, the bovine liver is an important regulator of circulating concentrations of insulin and glucagon.
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PMID:Net metabolism of hormones by portal-drained viscera and liver of lactating holstein cows. 266 59

We studied effects of changes in hepatic insulin influx on hepatic insulin retention. In order to compare insulin net flux (influx - efflux) with percentage (%) hepatic insulin extraction (net flux/influx X 100), as indices of hepatic insulin retention, we examined which index is better predicted by insulin influx to the liver. Electromagnetic hepatic blood flow measurements were made and blood was sampled from portal, hepatic and peripheral veins and femoral artery in anesthetized dogs. Insulin influx was perturbed by sequentially superimposed peripheral venous infusions of somatostatin, glucagon and insulin (which were subsequently discontinued one at a time). Although the somatostatin was biologically effective in inhibiting insulin and glucagon release we found no significant plasma flow changes on starting or stopping the infusion of somatostatin (800 ng X kg-1 X min-1). Net insulin flux was linearly related to influx (n = 56, r = 0.99, p less than 0.001). Hepatic glucose production was better correlated with net insulin flux (r = -0.66; p less than 0.01) than with % extraction (r = 0.08; N.S.), when mean glucagon influx was held constant (partial correlation). Although net insulin flux and % extraction are complementary indices, the former reflects influx changes more faithfully than the latter.
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PMID:The effect of hepatic insulin influx on insulin retention: comparison of net flux and per cent extraction as indices of hepatic insulin retention. 286 58


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