Plasma Somatostatin-like Immunoreactivity Research Articles

Insulin inhibits somatostatin-like immunoreactivity release stimulated by intragastric HCl.

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.

Plasma somatostatin-like immunoreactivity during the interdigestive period in the dog.

To study possible physiologic relationships between somatostatin and the gastric interdigestive contractions (GIC), gastric motor activity, and plasma somatostatin-like immunoreactivity (SLI) concentration were determined simultaneously in four conscious dogs, each of which was studied on two separate occasions. Plasma SLI level was highest during the GIC period and lowest 60 and 80 min after the cessation of the GIC; the mean difference in plasma SLI was 41 +/- 6 pg/ml. When synthetic motilin, a known stimulus of GIC, was infused at a physiologic rate during the period in which plasma SLI levels were low, SLI rose to approximately the same values observed during the contraction period and GIC similar to those that occur spontaneously were observed. When synthetic somatostatin, a known inhibitor of endogenous motilin release, was infused at a rate that raised the plasma SLI to approximately the levels observed during the contraction period (0.1 microgram/kg per h), the appearance of the subsequent GIC was significantly delayed. These results are consistent with a physiological role for somatostatin in the regulation of GIC in dogs and suggest an interrelationship between motilin and somatostatin.

Somatostatin-like immunoreactivity in human peripheral plasma measured by radioimmunoassay following affinity chromatography.

Somatostatin-like immunoreactivity (SLI) concentrations were determined in human peripheral plasma using affinity chromatography followed by radioimmunoassay. In normal subjects, fasting SLI ranged from 2.9 to 22.0 pg/ml with a mean +/- SE value of 10.2 +/- 2.1 pg/ml. In totally pancreatectomized or gastrectomized patients, fasting SLI levels were not different from the values in normal subjects. In patients with medullary thyroid carcinoma, fasting SLI ranged from 11.8 to 71.0 pg/ml with a mean of 29.3 +/- 12.3 pg/ml, which was significantly higher than normal values (P less than 0.01). Following meal ingestion, plasma SLI increased significantly in normal subjects from a basal level of 9.1 +/- 2.1 pg/ml to a peak value of 15.4 +/- 2.9 pg/ml (P less than 0.02). These results indicate that radioimmunoassay combined with affinity chromatography provides an accurate method of measuring SLI in human plasma.

High plasma free fatty acid levels contribute to the hypersomatostatinemia of insulin deficiency.

High plasma levels of free fatty acids (FFA) stimulate the secretion of splanchnic somatostatin, and both are elevated in insulin deficiency. To determine if the hypersomatostatinemia of insulin deficiency is secondary to high FFA levels, plasma somatostatin-like immunoreactivity (SLI) was measured in a group of insulin-deprived alloxan-diabetic dogs during nicotinic acid-induced lowering of their elevated plasma FFA to normal, and in a group of nondiabetic dogs during nicotinic acid-induced lowering of their FFA to subnormal values. In insulin-deprived diabetic dogs, nicotinic acid reduced plasma FFA from 1.07 +/- 0.2 (M +/- SE) mmol/L to 0.6 +/- 0.1 mmol/L (P less than 0.02), approximately the basal FFA level in normal dogs. This was accompanied by a significant decline in plasma SLI levels from a mean baseline of 247 +/- 15 pg/ml to a mean nadir of 199 +/- 10 pg/ml (P less than 0.005). The latter was, nevertheless, significantly above the basal SLI level of the nondiabetic dogs. In contrast, in normal dogs, nicotinic acid-induced reduction in FFA from 0.54 +/- 0.02 mmol/L to 0.24 +/- 0.03 mmol/L (P less than 0.001) was associated with only a small and inconsistent decrease in SLI. These findings suggest that the hypersomatostatinemia of insulin-deficient alloxan-diabetic dogs is, in part, secondary to high plasma FFA levels.

Effect of 2-deoxy-D-glucose on plasma somatostatin levels in conscious dogs.

The effects of 2-deoxy-D-glucose (2-DG) on plasma levels of somatostatin-like immunoreactivity (SLI) were examined in conscious normal dogs. After an iv infusion of 2-DG (400 mg/kg . h for 15 min), plasma SLI rose significantly from a mean baseline of 130 +/- 5 pg/ml (mean +/- SEM) to a mean peak of 204 +/- 25 pg/ml (P less than 0.005) at 25 min. Plasma insulin and glucagon also increased significantly. Atropine (200 microgram/kg . h for 35 min, iv) and hexamethonium (5 mg/kg, iv) markedly suppressed the SLI response to 2-DG, suggesting that it might be mediated, at least in part, by the autonomic nervous system. In contrast, the plasma insulin and plasma glucagon responses to this glucose analog were only slightly affected by atropine or hexamethonium pretreatment. Carbachol (0.2 mg, sc) caused a mean maximal increase in SLI of 43 +/- 14% (P less than 0.005) and atropine (200 micrograms/kg . h, iv) caused a mean maximal decrease of 25 +/- 2% (P less than 0.001) from the respective baseline levels. Plasma insulin and glucagon rose promptly after carbachol and were unchanged by atropine. To assess th contribution of 2-DG-stimulated gastric acid secretion in the 2-DG-induced SLI rise 2-DG was infused during the infusion of the H2-receptor antagonist cimetidine (3.0 mg/kg . h). Plasma SLI, nevertheless, increased significantly from a mean baseline of 112 +/- 6 pg/ml to a mean peak of 158 +/- 19 pg/ml (P less than 0.005) at 20 min, although the magnitude of the response was substantially reduced (P = NS). These observations suggest that in the conscious dog, 2-DG stimulates SLI secretion in part via cholinergic mechanism.

Effect of bombesin upon plasma somatostatin-like immunoreactivity, insulin and glucagon in normal and chemically sympathectomized dogs

The present study was designed to determine the effects of intravenously infused bombesin (10 ng/kg/min) upon basal and postprandial plasma somatostatin-like immunoreactivity (SLI), glucagon, insulin and triglyceride levels in normal ( n = 12 ) and chemically sympathectomized ( n = 11 ) dogs. Basal plasma SLI, glucagon and insulin levels rose significantly during the infusion of bombesin in the normal dogs, and this was not altered by chemical sympathectomy. Bombesin infusion enhanced the postprandial SLI response, while attenuating the postprandial glucagon response by 50% and the insulin response in the earlt postprandial phase of the meal. Sympathectomy did not significantly alter the basal levels of these polypeptides, but augmented the postprandial plasma SLI response during the first 90 min, and reduced the postprandial glucagon response during the infusion of bombesin. The postprandial insulin response was not affected by sympathectomy. In both normal and chemically sympathectomized dogs the rise in postprandial triglyceride levels was attenuated by bombesin infusion.

Effect of exogenous and endogenous prostaglandin E upon gastric endocrine function in dogs.

The effects of prostaglandin E2 (PGE2) and indomethacin- induced endogenous PGE deficiency upon basal and postprandial release of gastric somatostatin-like immunoreactivity (SLI), glucagon, and gastrin during the gastric phase of a meal were determined in anesthetized, laparotomized dogs. The infusion of PGE2 (1 μg/kg- min) elicited a sustained rise in antral vein and inferior vena cava plasma SLI levels and a transient SLI rise in the fundic vein. Antral vein and inferior vena cava gastrin decreased significantly during PGE2 infusion, while fundic vein and inferior vena cava glucagon rose significantly. Indomethacin infusion (2 mg/kg-h) elicited a significant decrease in basal SLI levels in the fundic and antral veins and in the inferior vena cava plasma and a significant increase in basal antral vein gastrin levels, but no change in basal inferior vena cava gastrin or in basal fundic vein or inferior vena cava glucagon levels. The effects of PGE2 infusion upon postprandial SLI, gastrin, and glucagon var...

Plasma somatostatin-like immunoreactivity in depancreatized dogs.

The present study was designed to determine the D cell response to ingested nutrients in totally depancreatized dogs. Basal levels of somatostatin-like immunoreactivity (SLI) averaged 135 ± 12 pg/ml in 7 depancreatized dogs and 146 ± 10 pg/ml in 30 controls (P = NS). In 7 conscious depancreatized dogs, an intragastric casein hydrolysate load elicited a small but significant rise of 20 pg/ml in peripheral venous plasma SLI levels during the first 60 min (P < 0.02); the incremental SLI (sum of the increments) during this period was 103 ±31 pg/ml, significantly less than the 278 ± 60 pg/ml in the normal control dogs (P < 0.05). In contrast to normal dogs, SLI did not rise in the depancreatized dogs in response to a fat-rich meat meal. After a liver meal, SLI levels rose by 30–40 pg/ml (P = NS) compared to the 80 pg/ml rise in the normal dogs. Gastric vein SLI levels were measured during laparotomy in six depancreatized and five control dogs after an intragastric load of casein hydrolysate. Antral vein SLI le...

Somatostatinoma Syndrome

Diabetes mellitus, steatorrhea, cholelithiasis and a tumor distorting the duodenum prompted a work-up for somatostatinoma in a 52-year-old man. The responses of pancreatic B-cells but not of A-cells to nutrient stimuli were inhibited, and growth-hormone release was suppressed, suggesting somatostatin resistance in some target tissues. Plasma somatostatin-like immunoreactivity ranged from 9000 to 13,000 pg per milliliter (normal: 88+/-8, mean +/- S.E.M.) and was distributed in four molecular forms, including free somatostatin. The primary tumor contained 5 microgram of somatostatin-like immunoreactivity per milligram of wet tissue, distributed in three of the molecular forms noted in plasma. Plasma calcitonin was also elevated (4650 pg per milliliter; normal: less than 120). Immunocytochemical studies showed that cells of the primary tumor contained somatostatin and calcitonin but no other peptide hormones. Only somatostatin was present in the metastases. Somatostatin was localized electron microscopically in all secretory granules, irrespective of size and shape, whereas calcitonin was present only within a single subpopulation of small granules in the same cells.

Response of plasma somatostatin-like immunoreactivity to the administration of alloxan in dogs.

The present study was designed to examine the effects of intravenously injected alloxan (75 mg/kg) upon plasma somatostatin-like immunoreactivity (SLI), glucagon (IRG), insulin (IRI) and glucose levels in 6 dogs. Within 2 hours of the injection of alloxan, SLI and IRI levels decreased significantly below their respective baselines, while IRG and plasma glucose concentrations increased. At 8 hours SLI levels had increased significantly by 55 pg/ml, together with a rise in IRI and a decrease in IRG and glucose concentrations. After 24 hours, marked hyperglycemia and hyperglucagonemia had developed whereas SLI levels were not different from preinjection values.

Evidence for a Role of Splanchnic Somatostatin in the Homeostasis of Ingested Nutrients*

Somatostatin was infused via the portal vein at a rate of 50 ng/min in a group of eight conscious dogs beginning 30 min before and continuing for 6 h after the ingestion of an 800-g fat-protein meal. The fasting and postprandial levels of plasma somatostatin-like immunoreactivity (SLI), insulin, glucagon, and triglycerides were compared with those during an intraportal infusion of saline as a control. In both groups, SLI rose significantly within 15 min of the ingestion of the meal, but during somatostatin infusion, mean peripheral vein levels of SLI ranged from 30-85 pg/ml above those of the saline control experiments. The postprandial rise in plasma triglycerides was reduced significantly below the control values at all points between 75-270 min, and this reduction was the result of lowered chylomicron levels. Neither fasting nor postprandial insulin or glucagon levels were significantly reduced by the somatostatin infusion. Intraportally infused somatostain also reduced portal vein xylose levels after an intragastric xylose load. The results are compatible with, but do not prove, a physiological role for somatostatin in the homeostasis of ingested nutrients.

Plasma levels of somatostatin-like immunoreactivity-independence of kidney function.

Plasma levels of somatostatin-like immunoreactivity (SLI) and gastrin were determined by radioimmunoassay in patients with varying degrees of renal dysfunction. The plasma SLI was not increased in patients with end-stage renal failure as compared to healthy controls. In patients with varying degrees of renal insufficiency no significant correlation was found between the plasma SLI and kidney function as estimated by the 51Cr-EDTA-clearance rate. In uraemic patients a significant inverse correlation was found between plasma SLI and plasma gastrin.

Half-Life of Somatostatin-Like Immunoreactivity in Canine Plasma*

Previous estimates of the half-life of synthetic somatostatin have been based upon the disappearance rate of 125I-labeled Tyr1-somatostatin. In the present study, the half-life of infused synthetic somatostatin was determined by RIA and compared with the duration of its suppressive action upon plasma insulin and glucagon. After the end of a 2-h infusion of somatostatin (500 ng/min), the radioimmunologically measured half-life was 1.82 min. The reappearance half-times for insulin and glucagon were 1.4 and 6.7 min, respectively. These data show that calculations of the half-life of somatostatin-like immunoreactivity in plasma may differ from estimates based on the duration of its biological activities, which may differ from one another.

The response of plasma somatostatin-like immunoreactivity to nutrients in normal and alloxan diabetic dogs.

Somatostatin-like immunoreactivity (SLI) was measured by RIA in the plasma of normal and severely alloxan diabetic dogs in the fasting state and after the administration of nutrients. The iv infusion of glucose for 6 h was associated with a small but significant decline in plasma SLI (162 ± 10 to 146 ± 9 pg/ml; P < 0.01). In nine alloxan diabetic dogs, the baseline SLI levels averaged 212 ± 16 pg/ml, significantly higher than normal (P < 0.005), and there was little or no change during glucose infusion. Intragastric glucose elicited only a small transient rise in SLI in normal dogs, while in the diabetic dogs, a significant change in SLI was not observed. Intragastric administration of casein hydrolysate to nine normal dogs was associated with a rise in plasma SLI from < 0.02). After a liver meal, SLI rose in normal dogs from 134 ± 7 to 190 ± 15 pg/ml within 30 min (P < 0.001) and in the diabetic dogs, it rose from 240 ± 20 to a 30-min level of 244 ± 33 pg/ml (P < 0.005). In normal dogs, a fat-protein mea...

Measurements of somatostatin-like immunoreactivity in plasma

The validity of measurements of somatostatin-like immunoreactivity (SLI) in canine plasma has been examined. The radioimmunoassay employed had a minimal sensitivity of 50 pg/ml and a discriminatory sensitivity of 15 pg/ml above this. The coefficient of variation within and between assays was 6% and 18%, respectively. There was no cross-reaction with any of 9 other peptide hormones tested. Significant incubation damage by canine plasma to the [ 125I]-tyrosine 1-somatostatin tracer was effectively prevented by Trasylol and EDTA, and recovery of synthetic somatostatin added to canine plasma and incubated for 3 h at 20°C was 96%. Subcutaneous injections of somatostatin were followed by a prompt rise in plasma SLI that was significantly correlated with decrease in plasma glucagon levels. Serial dilutions of plasma specimens containing high levels of either endogenous SLI or injected synthetic somatostatin gave proportional readings and their slopes paralleled those of synthetic somatostatin in plasma-free buffer. Ninety-five percent of endogenous plasma SLI was removed by passage of plasma specimens through a column of immobilized somatostatin antibodies. Both endogenous SLI in plasma and synthetic somatostatin added to plasma were eluted in the void volume of Biogel P-10 columns, but following isolation by affinity chromatography the molecular size of both was approx. 1600, suggesting that both endogenous SLI and synthetic somatostatin circulate in plasma bound to larger molecules. It is concluded that this radioimmunoassay permits valid measurements of endogenous SLI in canine plasma.