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 effects of inhibitors of insulin secretion on the concentration of plasma insulin and on the subcellular distribution of hepatic insulin receptors have been examined in rats. Liver plasma membranes, Golgi fractions, and a total particulate fraction were prepared various times after the injection of diazoxide (10 mg), xylazine (0.5 mg), and somatostatin (20 micrograms as a bolus followed by a 20 micrograms/15-min infusion), solubilized by Triton X-100, and examined for specific insulin binding. Injection of each of these drugs caused a 4- to 8-fold decrease in plasma insulin concentration, and concomitantly, a 25-35% decrease in insulin binding to Golgi fractions; a 10% increase in insulin binding to plasma membranes also occurred in diazoxide-treated rats. Insulin binding to the total particulate fraction was unaffected. These changes achieved maximum by 10-30 min and underwent complete reversal in 1 h. The decrease in insulin binding to Golgi fractions resulted exclusively from a change in receptor number and was accompanied by a 4- to 6-fold decrease in the content of extractable insulin in these fractions; the latter observation suggests that receptor internalization, rather than receptor synthesis, is diminished. The effects of diazoxide on plasma insulin concentration, insulin binding to Golgi fractions, and insulin content of Golgi fractions were fully prevented by tolbutamide, a stimulant of insulin secretion. These results show that acute hypoinsulinemias in rats are accompanied by changes in the subcellular distribution of hepatic insulin receptors that are opposite to those previously observed in acute hyperinsulinemias. Furthermore, both in acute hyperinsulinemic and hypoinsulinemic models, a significant correlation is observed between plasma insulin concentration on the one hand, and insulin binding to Golgi fractions as well as insulin content of Golgi fractions on the other. It is concluded that the extent to which hepatic insulin receptors are internalized is a function of their occupancy by endogenous hormone, and that, at least under acute conditions, receptor internalization is one major mechanism involved in receptor regulation.
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PMID:Insulin-related changes in the subcellular distribution of insulin receptors in intact rat liver: effects of acute hypoinsulinemia induced by diazoxide, somatostatin, and xylazine. 288 96

We attempted to improve the precision of the estimation of insulin sensitivity (S1) from the minimal model technique by modifying insulin dynamics during a frequently sampled intravenous glucose tolerance test (FSIGT). Tolbutamide and somatostatin (SRIF) were used to change the insulin dynamics without directly affecting insulin sensitivity. Injection of tolbutamide (100 mg) at t = 20 min provoked an immediate secondary peak in insulin response, resulting in a greater integrated incremental insulin than the standard FSIGT. SRIF, injected at t = -1 min, delayed insulin secretion in proportion to the dose without any change in magnitude. Computer simulation was used to assess the precision of S1 estimation. Insulin dynamics from both standard and modified protocols were adjusted in magnitude, with the shape unchanged and analyzed to determine the effect of the magnitude of insulin response. Fractional standard deviation was reduced from 73% with the standard insulin profile to 23% with tolbutamide and 18% with the highest dose of SRIF. In addition, the fractional standard deviation of S1 estimates decreased exponentially with increasing magnitude of insulin response. Modified FSIGTs require a smaller insulin response than the standard protocol to achieve the same precision.
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PMID:Modified protocols improve insulin sensitivity estimation using the minimal model. 289 14

The interhormonal relationship within the pancreatic islets have been studied by previous investigators, but the cellular interplay and the sequence of events in the islet cell's response to stimulators has remained unclear. In the present study, pancreatic islets were isolated by collagenase digestion from normal and streptozotocin-diabetic hamsters the latter being maintained with insulin treatment. The diabetic animals were used to provide A- and B-cell enriched islets. The islets from normal and diabetic hamsters were cultured in medium 199 plus 10% fetal calf serum with 0.8 or 5 mg/ml glucose. The cultures were maintained for up to seven days with medium changes every third day. At specified intervals, media were collected and assayed for insulin, glucagon and somatostatin. Our results showed the expected increased insulin secretion by the B-cells in response to high glucose. However, after two days of culture accumulative insulin secretory response was reduced and at the end of seven days was less than the insulin produced in low glucose medium. Glucagon secretion by the A-cells was similar for low and high glucose media for the entire culture period. Somatostatin secretion by D-cells was stimulated by high glucose but was attenuated after 2 days. No correlation could be found between the concentration of hormone in the media and a possible effect on a specific islet secretion. However, the fact that insulin secretion by islets cultured in high glucose was decreased after two days may indicate a refractoriness produced by persistent hyperglycemia. Islets isolated from diabetic animals secreted more glucagon and less insulin than control islets. Somatostatin secretion was the same in both groups. It was concluded that paracrine relationships were relatively insignificant in the regulation of islet secretion in a prolonged culture environment and persistent high glucose reduced the B-cell response to glucose stimulation.
Acta Diabetol Lat
PMID:Insulin, glucagon and somatostatin secretion by cultured islets from normal and diabetic hamsters. 289 3

Pancreastatin is a novel peptide, isolated from porcine pancreatic extracts, which has been shown to inhibit glucose-induced insulin release "in vitro". To achieve further insight into the influence of pancreastatin on pancreatic hormone secretion, we have studied the effects of this peptide on unstimulated insulin, glucagon and somatostatin output, as well as on the responses of these hormones to glucose and to tolbutamide in the perfused rat pancreas. Pancreastatin strongly inhibited unstimulated insulin release as well as the insulin responses to glucose and to tolbutamide. It did not significantly affect glucagon or somatostatin output under any of the above-mentioned conditions. These findings suggest that pancreastatin inhibits B-cell secretory activity directly, and not through an A-cell or D-cell paracrine effect.
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PMID:Effects of pancreastatin on insulin, glucagon and somatostatin secretion by the perfused rat pancreas. 289 8

Plasma membrane Ca2+-ATPase activity was measured in rat islet homogenates. The enzyme was inhibited, in a dose-dependent manner, when the islets were preincubated for 5 min with different concentrations of glucose (2 to 16 mM). This inhibition disappeared almost entirely after 15 min incubation, regardless of the glucose concentration in the medium. Simultaneous measurement of insulin in the medium revealed a stimulatory effect of glucose upon insulin secretion. The Ca2+-ATPase activity was also inhibited when the islets were preincubated for 3 min with other stimulators of insulin secretion such as gliclazide (76 microM), tolbutamide (1.5 mM), glucagon (1.4 microM) + theophylline (10 mM) and ketoisocaproic acid (15 mM). Conversely, the activity of the enzyme was significantly enhanced when the islets were preincubated briefly with the insulin secretion blocker, somatostatin (1.4 microM). Neither glucose nor any of the other substances tested when added directly to the enzyme assay medium modified significantly the Ca2+-ATPase activity measured in the islet homogenates. These results would suggest that the activity of the islet plasma membrane is modulated by one or more of the intracellular metabolites produced when the islets are challenged by the insulin stimulator or blocking agents.
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PMID:Effect of different insulin secretagogues and blocking agents on islet cell Ca2+-ATPase activity. 290 24

Salicylate compounds are known to increase basal and stimulated insulin secretion in man. In our studies, infusion of lysine acetylsalicylate (72 mg/min) increased basal insulin levels and amplified insulin responses to glucose (5 g i.v.), arginine (5 g i.v.) and tolbutamide (1 g i.v.). Verapamil, an organic calcium antagonist, did not modify LAS-induced increase of basal insulin levels, but reduced the effect of LAS on glucose-induced insulin secretion. Calcitonin and somatostatin, two agents that inhibit basal and glucose-stimulated insulin secretion, inhibited the insulin response to glucose in presence of LAS infusion. The ability of salicylate compounds to augment insulin secretion might be due to multiple sites of action in the Beta-cells.
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PMID:Studies on the mechanism of salicylate-induced increase of insulin secretion in man. 290 99

We have evaluated the potential of the clonal insulin-secretory cell line HIT-T15 as a model system for investigating stimulus-secretion coupling in pancreatic B cells. In contrast to other cell lines, HIT cell insulin secretion was consistently stimulated 2- to 3-fold by D-glucose. The maximally effective concentration of glucose was 10 mmol/l; between 2 and 10 mmol/l glucose the increase in insulin release was paralleled by an increased rate of glucose oxidation. The main characteristics of glucose-stimulated insulin release by HIT cells were essentially similar to those of normal islets. Thus, the response was specific for metabolizable sugars (D-mannose and D-glyceraldehyde stimulated insulin release but L-glucose and D-galactose were ineffective); markedly dependent on extracellular Ca2+ concentration; potentiated by forskolin, glucagon, acetylcholine and 12-O-tetradecanoyl phorbol 13-acetate; inhibited by adrenaline or somatostatin; showed a biphasic pattern of release in perifusion experiments, with both phases being potentiated by forskolin. The secretory response of the HIT cells to amino acids was also similar to that of normal islets. Thus, L-leucine and its deamination product 2-ketoisocaproate were effective stimuli, whereas L-isoleucine and L-glutamine were ineffective. Insulin release from HIT cells could also be evoked by the sulphonylureas glibenclamide and tolbutamide and by an increase in concentration of extracellular K+ to 40 mmol/l. The content of cyclic AMP in HIT cells was increased modestly by glucose but not by an increase in extracellular K+. Forskolin elicited a 4-fold increase in cyclic AMP content. We conclude that HIT cells retain the essential features of the insulin secretory response of normal B cells and represent an important tool for further biochemical characterization of the secretory system.
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PMID:Insulin secretory responses of a clonal cell line of simian virus 40-transformed B cells. 302 78

We describe a patient with a small somatostatinoma of the papilla of Vater without clinical evidence for diabetes mellitus, diarrhea, steatorrhea, or cholelithiasis, showing normal plasma basal levels for somatostatinlike immunoreactivity. The diagnosis was based on histologic and immunohistochemical analysis of tumor tissue and hypersomatostatinemia induced by the calcium-pentagastrin test. Before removal of the tumor both diagnostic tests recommended for the detection of a somatostatinoma, a tolbutamide test and a calcium-pentagastrin test, were performed. Whereas the calcium-pentagastrin test provoked a markedly elevated plasma somatostatin level in association with a depressed plasma neurotensin level, the tolbutamide test surprisingly did not. After removal of the tumor the calcium-pentagastrin test no longer induced hypersomatostatinemia. Further studies are needed to determine whether the calcium-pentagastrin test is a more reliable diagnostic test than the tolbutamide test in somatostatinomas with normal plasma basal levels.
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PMID:Comparative diagnostic value of the calcium-pentagastrin test versus the tolbutamide test in a patient with a somatostatinoma. 302 98

The fluorescent acridine derivative, quinacrine, was found to accumulate in rat and mouse pancreatic islet cells storing insulin, glucagon, pancreatic polypeptide, or somatostatin. Following administration of large doses of tolbutamide via an oro-gastric tube, the intensity of quinacrine fluorescence of insulin cells was substantially reduced. Similarly, the pancreatic insulin content was lowered. In contrast, the fluorescence intensity of the glucagon, pancreatic polypeptide and somatostatin cells appeared unaffected. Basal plasma insulin levels in the mouse were slightly elevated following quinacrine administration (25%). Glucose-stimulated insulin release was markedly enhanced (51%) in quinacrine-pretreated animals, whereas insulin release induced by cholinergic stimulation was unaffected. The results show that quinacrine accumulates in the various pancreatic islet cells. The drug seems to be confined to the secretory granules and affects the insulin response to glucose but not that to cholinergic stimulation, suggesting that these secretagogues act through different or partly different secretory pathways.
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PMID:Quinacrine accumulation in pancreatic islet cells of rat and mouse: relationship to functional activity and effects on basal and stimulated insulin secretion. 388 58

Based on the assumption that somatostatin may inhibit peptide release through junctional complexes or through local circulation, an immunfluorescent technique for somatostatin and GLI in the gut was applied in order to investigate whether suppression of GLI release by i.v. administration of somatostatin was a physiological effect of somatostatin or not. Somatostatin-immunoreactive cells (GIF-cells) in the human and canine intestine had no direct cellular contacts with GLI-immunoreactive cells (GLI-cells). This finding suggests that somatostatin in the intestine does not inhibit GLI release through junctional complexes between GIF- and GLI-cells. As to the local circulation, most of GIF-cells in the canine intestine were distributed in the deeper portion of the intestinal gland which corresponds to the upstream sides of the local blood supply of the intestinal gland, as reported by REYNOLD et al. The ratio of GIF-cells to total cells (GIF-cells + GLI-cells) was 68% in the duodenum and 25% in the ileum. In contrast a limited number of GIF-cells was found in the human duodenum where a few GLI-cells were distributed and a few GIF-cells were seen in the human ileum where a large number of GLI-cells were located. Findings in the dog suggest the possibility that somatostatin inhibits GLI release from GLI-cells through the local circulation system of intestinal glands. However, findings in humans suggest that the same possibility does not apply to the human gut. Differences of population density of intestinal GIF-cells between humans and dogs indicate that the functional meaning of GIF-cells may vary from one species to another.
Acta Diabetol Lat
PMID:Does somatostatin in the gut inhibit the GLI release locally? 610 41


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