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 present study was performed in order to evaluate the plasma glucose pattern in cirrhotic patients who, in the course of a continuous somatostatin infusion (500 microgram/h), were given pulses of glucagon (1 mg i.v.). In normal as well as in cirrhotic subjects somatostatin infusion provoked a marked reduction of the IRI plasma level and this was uninfluenced by subsequent glucagon administration. The rise in plasma glucose level in response to i.v. glucagon administration during somatostatin infusion was less marked in cirrhotics compared to normal subjects. This can be attributed to a variety of factors such as reduced number of liver cells or quantitative or qualitative changes of the liver cell glucagon receptors. Glucagon does not seem to contribute to the pathogenesis of carbohydrate intolerance in liver cirrhosis.
Acta Diabetol Lat
PMID:Effect of somatostatin (SRIF) on plasma glucose and insulin response to glucagon in liver cirrhosis. 48 63

In four patients with organic hyperinsulinism (two with surgically proven beta-cell adenomas of the body of the pancreas) a standard tolbutamide test during continuous somatostatin infusion (5 microgram/min) was carried out. Tolbutamide induced insulin release was completely inhibited by somatostatin as in normal subjects. These results suggest that the inhibition test with somatostatin does not seem to be a better or safer way of diagnosing insulin producing tumours.
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PMID:Failure of somatostatin to diagnose organic hyperinsulinism. 62 95

The nature and extent of somatostatin-induced inhibition of pancreatic endocrine secretion were studied by administration of a number of stimuli of either glucagon or insulin to over night fasted baboons with and without an infusion of linear somatostatin. The stimuli for acute-phase insulin release were intravenous pulses of glucose, tolbutamide, isoproterenol, and secretin. When given 15 min after the start of a somatostatin infusion, these agents were essentially unable to stimulate insulin secretion. Chronic insulin secretion was stimulated by infusions of either glucose or glucagon. Within 10 min of the start of a super-imposed infusion of somatostatin, insulin levels fell to less than 40 percent of prestimulus control and remained suppressed for the duration of the somatostatin infusion. Stimulation of glucagon secretion by insulin-induced hypoglycemia was also blocked by somatostatin. Plasma glucose decreased during somatostatin infusions except when superimposed upon an infusion of glucagon. Somatostatin had no effect on glucose production in a rat liver slice preparation. We conclude: (a) Somatostatin is a potent and so far universally effective inhibitor of both acute and chronic phases of stimulated insulin and glucagon secretion (b) The inhibitory effect is quickly reversible and the pattern of recovery of secretion is appropriate to prevailing signals; (c) Present evidence suggests that the effect of somatostatin on blood glucose is mediated through its effect on blood glucagon; (d) In the overnight-fasted baboon both in the basal state and 45 min into a 4-mg/kg-min glucose infusion, a somatostatin-induced fall in serum insulin levels appears to be unable to prevent a decrease in hepatic glucose production.
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PMID:Somatostatin blockade of acute and chronic stimuli of the endocrine pancreas and the consequences of this blockade on glucose homeostasis. 80 91

True or 'pancreatic' glucagon-like immunoreactivity (GLI) was found in the plasma of a pancreatectomized patient. In contrast with the regulation of pancreatic GLI in normal controls, there was paradoxical release after oral glucose, no response to arginine or insulin-hypoglycaemia and somatostatin did not suppress its release, but tolbutamide did. Similar to controls, this pancreatic GLI appeared to be under adrenergic beta-receptor control. There was no apparent effect on blood glucose regulation despite marked changes in pancreatic GLI levels during the various manipulations. On polyacrylamide gel electrophoresis, pancreatic GLI from our patient's plasma eluted as two equivalent peaks: one with the glucagon marker and the other in a more cathodal position. We therefore suggest that, although the extra-pancreatic 'pancreatic' GLI in our patient's plasma has immunologic similarities with pancreatic glucagon, the responses to stimulation and suppression are quite different from those in controls and the biologic activity does not appear to be that of pancreatic glucagon.
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PMID:Pancreatic glucagon-like immunoreactivity in a pancreatectomized patient. 88 71

This neonate developed marked hyperglycemia four days after birth and required insulin therapy for eight weeks. During the acute phase of the disease, immunoreactive insulin was undetectable in portal venous serum. Neither tolbutamide nor theophylline administration significantly triggered insulin secretion. Somatostatin infusion inhibited growth hormone release but had no effect on plasma glucagon or blood glucose concentrations. At 2 1/2 months, two weeks after insulin withdrawal, the infant was still intolerant to an oral glucose load, insulin response was markedly delayed, and growth hormone secretion was paradoxical. At five months, the insulin, glucagon, and growth hormone responses to glucose and to somatostatin were normalized. Thus, in this patient, insulin secretion was transiently deficient. Peculiarities of glucagon and growth hormone secretion were also present but are more characteristic of this age group than of diabetes. The hyperglycemic state was managed by intraportal infusion of 0.1 to 0.2 IU regular insulin/kg/hour. This mode of insulin administration proved efficient, secure, and easy to manage.
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PMID:Transient diabetes mellitus in a neonate. Evaluation of insulin, glucagon, and growth hormone secretion and management with a continuous low-dose insulin infusion. 89 7

Somatostatin in as small a dose as 70 mug given over a period of 90 min to seven healthy subjects inhibited insulin release induced by glucose (500 mg/kg as a bolus + 20 mg/kg/min). This inhibition seemed to be of competitive nature since the effect was nearly overcome when the glucose dose was raised considerably. Somatostatin in nine subjects also inhibited insulin release induced by glucagon and tolbutamide, and this inhibition was of the same order of magnitude as that of glucose induced insulin release. Since all these insulinogogues enhance of the accumulation of cyclic AMP in the beta-cells, it is suggested that the edenylate cyclase-cylic AMP system might be involved in the action of somatostatin. Somatostatin did not seem to interfere with the glycogenolytic effect of glucagon on the liver.
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PMID:Studies on the mechanism of somatostatin action on insulin release in man. II. Comparison of the effects of somatostatin on insulin release induced by glucose, glucagon and tolbutamide. 94 64

Somatostatin inhibited insulin secretion stimulated by glucose, tolbutamide, glucose-theophylline, glucose-cytochalasin B, and calcium in monolayer cell cultures of neonatal rat endocrine pancreas. Both 2-deoxyglucose-inhibited glucose-induced insulin release and basal insulin secretion occurring at glucose 1.7 mM were further reduced by somatostatin. In the presence of somatostatin, 1.0 mug/ml, insulin secretion due to glucose, tolbutamide, or glucose-cytochalasin B were inhibited to levels below the basal secretion seen with glucose 1.7 mM. However, insulin secretion stimulated by calcium, and especially by glucose plus theophylline, remained considerably above basal insulin levels, even with somatostatin 1.0 mug/ml. For all stimuli except calcium, at lower concentrations of somatostatin (0.001-0.10 mug/ml) but not at somatostatin 1.0 mug/ml, increased stimulus concentration partially reversed inhibition by somatostatin. For calcium, even at somatostatin 1.0 mug/ml, insulin release was greater when the calcium concentration was raised. Since net calcium uptake by the beta cell or intracellular translocation of calcium within the beta cell from an organelle-bound pool to a cytoplasmic pool may trigger insulin secretion through interaction of calcium with the microtubular-microfilamentous system, we suggest that the inhibition by somatostatin of calcium influx would explain our findings.
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PMID:Somatostatin inhibition of glucose-, tolbutamide-, theophylline, cytochalasin B-, and calcium-stimulated insulin release in monolayer cultures of rat endocrine pancreas. 110 17

The effect of low-dose somatostatin (2.5 mug/min i.v.) on blood sugar, insulin and GH levels (basal and after i.v. 1 mg glucagon) was studied in 7 normal and 10 acromegalic subjects. No changes in basal values were noted in normal subjects, whereas the insulin response to glucagon was partly inhibited and the glucose response enhanced. Basal blood glucose was likewise unaltered in the acromegalics. There was, however, a significant, though unrelated, fall in both insulin and GH. The insulin response to glucagon was inhibited to a greater degree than in normal subjects. It is clear, therefore, that somatostatin can inhibit the insulin response to glucagon, as well as that to the other stimuli for which data are given in the literature. Acromegalic subjects appear to be more sensitive to inhibition of insulin secretion by somatostatin, though no relation between this and the drug's parallel inhibition of GH secretion can be shown.
Acta Diabetol Lat
PMID:The effect of somatostatin on plasma insulin and growth hormone levels in basal conditions and after glucagon in normal and acromegalic subjects. 122 5

A case of duodenal somatostatinoma is described in a patient with Von Recklinghausen neurofibromatosis. The patient presented with exocrine pancreatic insufficiency, probably due to distal obstruction of the pancreatic duct by the tumor. Preoperative evaluation with calcium-pentagastrin and tolbutamide stimulation tests were nondiagnostic. At laparotomy, local excision of the tumor was performed. Pathological findings were compatible with duodenal somatostatinoma, causing pancreatic fibrosis. Somatostatin extracted from the tumor coeluted with the somatostatin-14 standard on high performance liquid chromatography (HPLC).
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PMID:Exocrine pancreatic insufficiency and pancreatic fibrosis due to duodenal somatostatinoma in a patient with neurofibromatosis. 134 57

Ionic and electrical events play a central role in the stimulus-secretion coupling of the pancreatic B cell. Potassium permeability is critically involved in the regulation of B cell membrane potential and insulin secretion. In the absence of glucose, membrane potential remains stable, around -65 mV. This resting potential is mainly determined by the high potassium conductance of the membrane. The ATP generated by glucose metabolism in B cells blocks the K+(ATP) channels controlling resting membrane potential. Thus, glucose metabolism leads to closure of the ATP-dependent potassium channels; the resulting decrease in K+ permeability induces depolarization and opening of voltage-activated Ca-channels. The subsequent increase in Ca2+ influx raises the cytoplasmic concentration of free Ca2+, which in turn triggers exocytosis of secretory granules. Other types of K+ channels have also been identified in the B cell, such as voltage- and Ca(2+)-dependent K+ channels, which are not a target for the action of glucose, but may play a role in the repolarization of spikes. The modulation of insulin release by some hormones and neurotransmitters involves, among other mechanisms, an interference with the plasma membrane K+ conductance. Thus, galanine, somatostatin and adrenaline, which inhibit insulin release, increase K+ conductance by a G protein-dependent mechanism; both peptides were reported to open ATP-sensitive K+ channels in insulin-secreting cell line RINm5F. It was also observed that extracellular purine nucleotides could interfere with K+ channels. Among the various drugs interfering with insulin secretion, sulfonylureas, such as tolbutamide and glibenclamide, directly inhibit ATP-dependent K+ channels in the B cell membrane and thereby initiate insulin release. In contrast, potassium channel openers such as diazoxide, antagonize the effects of glucose by increasing K+ permeability of the B cell membrane. Furthermore, other classes of drugs have recently been shown to interact with K+ (ATP) channels. Thus, K+ channels of the pancreatic B cell, particularly ATP-dependent ones, play a crucial role in the electrophysiology of insulin secretion; they are an important target for pharmacological agents designed to modulate this secretion.
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PMID:Potassium channels of the insulin-secreting B cell. 162 75


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