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)

In order to differentiate the roles of hyperinsulinemia and hyperglycemia per se in the homeostatic response to i.v. glucose administration, two groups of normal subjects were given either glucose alone (3.5 mg kg-1 min-1) or glucose (3 mg kg-1 min-1) in conjunction with somatostatin (500 microgram hr-1), insulin (0.15 mU kg-1 min-1) and glucagon (1 ng kg-1 min-1). Glucose kinetics were measured by the primed-constant infusion of 3-3H-glucose. During the infusion of glucose alone, plasma glucose stabilized at levels 45--50 mg/dl above the fasting values. Endogenous glucose output was markedly suppressed by 85%--90% while glucose uptake rose to values very close to the infusion rate of exogenous glucose. Glucose clearance remained unchanged. Plasma insulin rose to three-fourfold while plasma glucagon fell by 25%--30%. When glucose was infused with somatostatin, insulin, and glucagon, plasma insulin was maintained at levels 50% above baseline while glucagon remained at preinfusion levels. Under these conditions, the infusion of exogenous glucose resulted in a progressive increase of plasma glucose which did not stabilize until the end of the study period (190 mg/dl at 120 min). Endogenous glucose production was consistently suppressed (52%) but significantly less than observed with the infusion of glucose alone (p less than 0.01). Glucose uptake increased to the same extent as with glucose alone, despite the more pronounced hyperglycemia. Thus, glucose clearance fell significantly below baseline (25%--30%; p less than 0.01). These data demonstrate that hyperglycemia per se (fixed, near basal levels of insulin and glucagon) certainly contributes to the glucoregulatory response to i.v. glucose administration by both inhibiting endogenous glucose output and increasing tissue glucose uptake. However, the extra-insulin evoked by hyperglycemia is necessary for the glucoregulatory system to respond to the glucose load with maximal effectiveness.
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PMID:The glucoregulatory response to intravenous glucose infusion in normal man: roles of insulin and glucose. 611 55

Oral glucose tolerance tests (g 1/kg body weight were performed in 14 high diabetic risk subjects (mean age: 39,5 years), 9 insulin-dependent diabetic patients (mean age: 37,8 years) and 14 normal subjects (mean age: 31,5 years). Glucose, IRI and IRG were determined at various intervals. In the high diabetic risk subjects: 1) the OGTT was normal; 2) the insulin response to carbohydrate ingestion was significantly higher than in normals and, of course, in diabetics; 3) the fasting glucagon levels showed no significant differences from the normals; 4) significant suppression of fasting glucagon concentration was observed in normals after oral glucose, but not in high diabetic risk subjects and in diabetic patients. On the basis of our findings it might be suggested, therefore, that in the subjects, who are genetically pre disposed to developing diabetes mellitus, insulin does not suppress pancreatic glucagon secretion or owing to a functional disorder among alpha- beta- and delta-cells, somatostatin secretion is deficient or slow with following hyperinsulinemia and hyperglucagonemia.
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PMID:[The response of pancreatic alpha and beta cells to oral glucose stimulation in subjects with risk of diabetes]. 611 18

A new era has been started in the morphological research of the human pancreatic islet parenchyma by the introduction of immunohistochemical (IHC) and modern morphometric techniques. This statement is illustrated by a report of two infants from two families with persistent neonatal hypoglycemia with hyperinsulinism, where specimens of pancreas, obtained at subtotal pancreatectomy, were analyzed together with autopsy specimens from age-matched "controls" (cardiac malformations). It was found that a nesidioblastosis-like picture occurred in the pancreas of the "controls", at least up to 6-7 months of age, and that in IHC stained sections this was indistinguishable from that observed in the endocrine pancreas of the hypoglycemic infants. Moreover, there was no difference in the total volume density of the islet parenchyma in pancreas of controls and hypoglycemic children when analyzed by morphometry. However, an increase in the relative incidence of insulin cells was found in the hypoglycemic infants as well as a moderate reduction of glucagon cells and a marked decrease of somatostatin cells. Clinically, some alleviation of the symptoms could be obtained by administration of glucagon and somatostatin, indicating that the hypothesis is correct that a defect in the maturation of the islet parenchyma during infancy may be a main pathogenetic factor in the syndrome. The familial occurrence of the disease may be more common than previously realized.
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PMID:Immunohistochemical, morphometric, and clinical studies of the pancreatic islets in infants with persistent neonatal hypoglycemia of familial type with hyperinsulinism and nesidioblastosis. 611 6

To determine the effect of an increase in insulin levels within the range occurring under physiologic conditions on the protein- and acid-induced release of splanchnic somatostatin, insulin was infused in dogs for 1 h following the intragastric instillation of a neutral protein load (20% liver extract at pH 7), a weak stimulus of somatostatin-like immunoreactivity (SLI), and after an intragastric HCl, a strong stimulus of SLI release, instilled 30 min later. Insulin levels between 50 and 60 microunits/ml significantly reduced the rise in peripheral venous SLI levels elicited by the acid load from a mean integrated incremental value of 1705 +/- 182 pg/ml in controls to 840 +/- 312 in the insulin-infused group (P less than 0.05). Prevention of the insulin-induced hypoglycemia and the secondary rise in glucagon, a known stimulus of pancreatic somatostatin secretion, by means of a concomitant infusion of glucose, did not modify the reduction in acid-induced increase in plasma SLI concentration associated with hyperinsulinemia. Insulin-glucose infusion significantly lowered the SLI in the pancreaticoduodenal vein, and in the gastroepiploic vein draining the antrum (P less than 0.02; P less than 0.05), but not in the short gastric veins draining the fundus of the stomach in response to the acid load. It is concluded that physiologic elevation of insulin levels causes significantly reduced response of SLI to an intragastric acid load in dogs. This reduction is explained by a diminished increment of SLI in the venous effluent of the pancreas and the antrum.
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PMID:Insulin inhibits somatostatin-like immunoreactivity release stimulated by intragastric HCl. 611 88

A comparison of the somatostatin with the insulin and glucagon secretions in hypothalamic obesity and genetic obesity was made using the isolated perfused pancreas of rats. In our perfusion experiment, the somatostatin response to 19 mM arginine in the presence of 4.4 mM glucose was significantly greater in both ventromedial hypothalamus (VMH)-lesioned and Zucker fa/fa rats than in their controls, as was the perfusate insulin. The perfusate arginine-stimulated glucagon secretion appeared no different in obese and control rats. Because hyperinsulinemia in vivo and hyperresponses to arginine of perfusate insulin and somatostatin were observed in both VMH-lesioned and Zucker fa/fa rats, whereas the perfusate glucagon secretion in the presence of 4.4 mM glucose was unchanged by obesity, the secretory behavior of some pancreatic hormones seems similar in VMH-lesioned and Zucker fa/fa rats in certain conditions. These results suggest that some abnormalities of pancreatic hormone secretion may be caused by a mechanism common to obesity, whether caused experimentally or genetically.
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PMID:Somatostatin, insulin, and glucagon secretion from isolated perfused pancreas of obese rats. 611 83

Percutaneous transhepatic sampling of blood in the portal venous system (TPVS) was used to; (1) localize hormone secreting tumors and help in differentiating tumors from diffuse disease (nesideoblastosis and hyperplasia with adenomata) in 9 patients with fasting hypoglycemia and hyperinsulinism, and (2) study the concentration an distribution of the immunoreactive peptides: insulin (IRI), gastrin (IG), glucagon (IRG), pancreatic polypeptide (hPP), and somatostatin (SRIF-LI), in the venous drainage of the uninvolved portion of the pancreas and GI tract. Localized elevations of IRI (64-920 microunits/ml) predicted tumor localization in 6 patients with single tumors that were not demonstrable angiographically. In one patient with nesideoblastosis and another with islet cell hyperplasia with adenoma, elevated IRI concentrations at multiple locations suggested a diffuse or multicentric process. Elevations of SRIF-LI in the same region as IRI elevations in one patient and of IRG in another patient suggested that these tumor produced two hormones. Some problems in the interpretation of portal venous insulin concentrations are discussed. The locations of maximum portal venous system plasma concentrations and portal-arterial gradients (mean +/- SE pg/ml) in five patients with small single insulinomas were: IG, gastrocolic trunk (126 +/- 27, 46 +/- 22); IRG, proximal splenic vein (130 +/- 30, 47 +/- 13) and gastrocolic trunk (131 +/- 23, 60 +/- 13); hPP, portal vein (164 +/- 48, 49 +/- 22); SRIF-LI, superior mesenteric vein (186 +/- 50, 57 +/- 20) and gastrocolic trunk (178 +/- 59, 55 +/- 21). It is concluded; (1) TPVS can be used successfully to localize single insulin-secreting tumors of the pancreas and to help distinguish them from diffuse disease but problems in such differentiation do occur, (2) circulating SRIF-LI and IRG are derived from both the pancreas and the gut, IG predominantly from the proximal gut and hPP from the head of the pancreas, and (3) The data provide new information for the interpretation of portal insulin concentrations in patients with organic hyperinsulinism and of hormone concentrations for localization of peptide-producing tumors of the pancreas other than insulinomas.
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PMID:Gastrointestinal/pancreatic hormone concentrations in the portal venous system of nine patients with organic hyperinsulinism. 611 52

The method of administration of [D-Ala5,D-Trp8] somatostatin is of central importance in determining the degree and duration of suppression of insulin and glucagon release. The analog decreased insulin levels in rats when injected by s.c. or i.v. routes, with a nadir 15 minutes following injection. After i.v. injection, insulin levels rapidly returned to basal values while s.c. injection produced significant suppression for 60 minutes. Neither type of injection altered glucagon levels. Intravenous infusion resulted in inhibition of both insulin and glucagon release, with rebound hyperglucagonemia, but not hyperinsulinemia in the post-infusion period. Plasma glucose levels reflected these hormonal changes. Thus, dramatic alterations in the specificity of this somatostatin analog may be achieved by employing different methods of administration.
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PMID:Route of administration as a factor in the selectivity of hormone suppression of a somatostatin analog in rats. 611 82

The hypoglycaemia of infantile hyperinsulinism is often exceedingly difficult to control. The use of somatostatin has been advocated recently in such infants because of its effect on inhibiting insulin release, but nothing is known of the wider effects of this potent hormone in the young child. Two infants presenting at 9 weeks and 5 days of age with severe hyperinsulinaemic hypoglycaemia were studied during an infusion of somatostatin. In both infants normoglycaemia was restored with suppression of insulin secretion. An increase in blood ketone bodies occurred, but no change was seen in blood pyruvate, lactate or alanine concentrations. The plasma concentrations of glucagon, cortisol, growth hormone, motilin, pancreatic polypeptide, gastric inhibitory of polypeptide, neurotensin, gastrin and vasoactive intestinal peptide decreased markedly during the somatostatin infusion. No consistent change occurred in plasma enteroglucagon or secretin values. We conclude that somatostatin effectively suppresses abnormal insulin secretion in infants, but it has profound effects on the release of nine other hormones. Further studies are needed to define the consequences of suppressing the release of these hormones before somatostatin can be used routinely in the management of infantile hyperinsulinism.
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PMID:Effect of somatostatin infusion on intermediary metabolism and entero-insular hormone release in infants with hyperinsulinaemic hypoglycaemia. 611 71

To study the effect of insulin on leucine kinetics, three groups of conscious dogs were studied after an overnight fast (16-18 h). One, saline-infused group (n = 5), served as control. The other two groups were infused with somatostatin and constant replacement amount of glucagon; one group (n = 6) received no insulin replacement, to produce acute insulin deficiency, and the other (n = 6) was constantly replaced with 600 muU/kg per min insulin, to produce twice basal hyperinsulinemia. Hepatic and extrahepatic splanchnic (gut) balance of leucine and alpha-ketoisocaproate (KIC) were calculated using the arteriovenous difference technique. l,4,5,[(3)H]Leucine was used to measure the rates (micromoles per kilogram per minute) of appearance (Ra) and disappearance (Rd), and clearance (Cl) of plasma leucine (milliliters per kilogram per minute). Saline infusion for 7 h resulted in isotopic steady state, where Ra and Rd were equal (3.2+/-0.2 mumol/kg per min). Acute insulin withdrawal of 4-h duration caused the plasma leucine to increase by 40% (P < 0.005). This change was caused by a decrease in the outflow of leucine (Cl) from the plasma, since Ra did not change. The net hepatic release of the amino acid (0.24+/-0.03 mumol/kg per min) did not change significantly; the arterio-deep femoral venous differences of leucine (-10+/-1 mumol/liter) and KIC (-12+/-2 mumol/liter) did not change significantly indicating net release of the amino and ketoacids across the hindlimb. Selective twice basal hyperinsulinemia resulted in a 36% drop in plasma leucine (from control levels of 128+/-8 to 82+/-7 mumol/liter, P < 0.005) within 4 h. This was accompanied by a 15% reduction in Ra and a 56% rise in clearance (P < 0.001, both). Net hepatic leucine production and net release of leucine and KIC across the hindlimb fell markedly. These studies indicate that physiologic changes in circulating insulin levels result in a differential dose-dependent effect on total body leucine metabolism in the intact animal. Acute insulin withdrawal exerts no effect on leucine rate of appearance, while at twice basal levels, insulin inhibited leucine rate of appearance and stimulated its rate of disappearance.
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PMID:Role of insulin in the regulation of leucine kinetics in the conscious dog. 612 47

In an attempt to define the relationship between plasma insulin and triglyceride concentrations, we have studied the effect of suppression of the postprandial insulin response upon the secretion and plasma concentration of very low density lipoprotein (VLDL)-triglycerides. Eight nondiabetic subjects with a wide range of fasting plasma triglyceride levels (100-358 mg/dl) were studied during three dietary periods: base line, high carbohydrate (80% calories), and high carbohydrate (80% calories) with a daily intravenous infusion of somatostatin (SRIF) (1.3 micrograms/min) between 800 and 2,100 h. The significant increase in postprandial insulin response observed during high carbohydrate vs. base line was completely abolished during high carbohydrate-SRIF. However, plasma triglyceride levels rose in all subjects during each high carbohydrate period (with/without SRIF) vs. base line and the mean values reached during each period were the same (476 +/- 165 vs. 482 +/- 152 mg/dl, respectively). The secretion of VLDL-triglyceride into plasma was higher in four subjects, the same in two subjects, and lower in one subject during high carbohydrate-SRIF vs. high carbohydrate alone. The mean production rate of VLDL-triglyceride (mg/kg per h) was 25.6 +/- 4.9 during the high carbohydrate and 40.9 +/- 28.1 during the high carbohydrate-SRIF periods. These values were not significantly different. Postprandial glucose levels were slightly increased during high carbohydrate-SRIF, but overnight glucose concentrations were not affected. Plasma FFA levels were not different during the two high carbohydrate periods. Plasma glucagon levels did not appear to affect the results either. This study indicates that postprandial hyperinsulinemia during a high carbohydrate diet is not necessary for induction of hypertriglyceridemia.
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PMID:Effect of somatostatin-induced suppression of postprandial insulin response upon the hypertriglyceridemia associated with a high carbohydrate diet. 612 60


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