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)

Oral glucose tolerance tests (OGTT) were performed for two subsequent days in 4 patients with active acromegaly, 2 patients with prolactin-producing pituitary adenomas and one insulinoma patient. Thirty minutes before the second OGTT 250 mug of somatostatin were injected intravenously as a bolus followed by a somatostatin infusion (500 mug) over 21/2 hours. The OGTTs were pathologic due to the hGH- and hPRL-induced insulin antagonism; they could not be normalized or improved by somatostatin. Only the peak of the blood sugar curve was shifted from one to two and a half hours after glucose administration; insulin and hGH levels were regularly suppressed after somatostatin whereas hPRL remained unchanged in most instances. Gastrin levels increased in all patients during the OGTT, the increase was suppressed in 4 patients. These findings show that the pathologic glucose tolerance due to insulin antagonism could not be improved by somatostatin in contrast to the deteriorated glucose tolerance in insulinopenic states.
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PMID:[Influence of somatastatin on oral glucose tolerance in autonomous hypersecretion of growth hormone, prolactin or insulin (author's transl)]. 17 8

Pancreas and gut hormones are involved in many endocrine and gastrointestinal diseases. Radioimmunoassays for these hormones have proved particularly valuable in diagnosis, localisation and control of treatment of endocrine tumours, of which many are mixed. An estimate based on ten years experience in a homogenous population of 5 million inhabitants (Denmark) suggests, that endocrine gut tumour-syndromes on an average appear with an incidence of 1 patient per year/syndrome/million. At present six different syndromes are known: 1) The insulinoma syndrome, 2) The Zollinger-Ellison syndrome.3) The Verner-Morrison syndrome. 4) The glucagonoma syndrome. 5) The somatostatinoma syndrome, and 6) the carcinoid syndrome. Accordingly diagnostically valuable RIAs for pancreas and gut hormones include those for insulin, gastrin, VIP, HPP, glucagon, somatostatin, and presumably also substance P. It is probably safe to predict that the need for gut and pancreas hormone RIAs within the next decade will increase greatly in order to assure proper management of tumours producing gastroentero-pancreatic hormones.
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PMID:Radioimmunoassay in diagnosis, localization and treatment of endocrine tumours in gut and pancreas. 22 84

Effects of somatostatin on fasting and arginine-or tolbutamide-stimulated insulin release were studied in four patients with insulinoma. Somatostatin (bolus or bolus + infusion) reduced fasting insulin values in all patients; insulin response to tolbutamide was partially reduced in two patients; somatostatin bolus impaired the insulin response to arginine. Fasting glucagon levels and glucagon response to arginine were also reduced by somatostatin. These results indicate the potential usefulness of somatostatin in the diagnosis of insulinoma even if its effect on insulin is only partial.
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PMID:Effects of somatostatin on insulin and glucagon in patients with insulinoma. 23 Oct 62

With the aid of an artificial beta-cell (Biostator, Miles Laboratories Inc.), a different metabolic and biological pattern of behaviour was observed in benign versus malignant insulinoma. In the patient with beta-cell adenoma but not in the one with carcinoma, plasma insulin concentrations decreased promptly and markedly, and blood glucose increased during diazoxide and somatostatin infusion. Moreover, only in the adenoma patient was glucose need characterized by a circadian rhythm with the maximum values during daytime. This behavior could reflect the degree of tumor beta-cell differentiation. The controlled glucose and insulin infusion was of great help during and after surgical treatment.
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PMID:Artificial beta-cell application in two cases of insulinoma: a different pattern in beta-cell adenoma and carcinoma. 23 68

The endocrine function of the pancreas consists of the promotion of storage of nutritive substances after meals through the liberation of insulin and to guarantee the mobilization of this food energy through the secretion of glucagon during fasting. Increased hormone production may result from tumors of the islet cells (insulin: insulinoma; glucagon: glucagonoma; gastrin: Zollinger-Ellison syndrome). An absolute or relative insulin deficiency is a characteristic of diabetes mellitus, in which a relative hyperglucagonemia is also of possible pathophysiological significance. This increased secretion of glucagon can be suppressed by somatostatin. While the clinical application of somatostatin in diabetes mellitus seems problematic at present, the use of a glucose-controlled system of insulin infusion ("artificial pancreas") makes possible a metabolic state approaching the healthy condition.
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PMID:[The endocrine pancreas. From the isolated islet to the "artificial pancreas" (author's transl)]. 81 14

Vasoactive intestinal polypeptide (VIP)-immunoreactive nerves have been demonstrated in close association with the islets of Langerhans, and VIP has been shown to stimulate insulin and somatostatin secretion. Using [125I]VIP and membranes prepared from rat insulinoma (RIN) cells, i.e., the subclones m5F (m5F; mainly insulin-secreting) and 14B (14B; mainly somatostatin-secreting), it was found that VIP (10(-10)-10(-7) M) competitively inhibited the binding of [125I]VIP. A single class of high affinity binding sites with Kd values of 0.40 +/- 0.06 nM and 0.36 +/- 0.08 nM for m5F and 14B, respectively, with a corresponding number of binding sites (Bmax) of 163 +/- 20 and 254 +/- 51 fmol/mg protein was observed. The rank order of potency in inhibiting [125I]VIP binding was in both cell lines: VIP greater than helodermin greater than pituitary adenylate cyclase activating polypeptide 1-27 (PACAP27) greater than peptide histidine isoleucine (PHI) greater than secretin. VIP caused a dose-dependent increase in cAMP-formation in both m5F and 14B cell membranes with EC50 values of 3.0 and 3.5 nM, respectively, but VIP (1.10(-9)-3.10(-6) M) had no effect on insulin secretion (over 2 h) from the m5F cells. Thus, the data suggest that the VIP-receptors in these neoplastic rat cell lines, despite an apparent coupling to adenylate cyclase activity, seem to be functionally uncoupled to an effect on insulin secretion following an acute exposure to VIP.
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PMID:Demonstration of [125I]VIP binding sites and effects of VIP on cAMP-formation in rat insulinoma (RINm5F and RIN14B) cells. 133 38

Nitric oxide has recently been implicated as the effector molecule that mediates IL-1 beta-induced inhibition of glucose-stimulated insulin secretion and beta-cell specific destruction. The pancreatic islet represents a heterogeneous cell population containing both endocrine cells (beta-[insulin], alpha-]glucagon], gamma[somatostatin], and PP-[polypeptide] secreting cells) and non-endocrine cells (fibroblast, macrophage, endothelial, and dendritic cells). The purpose of this investigation was to determine if the beta-cell, which is selectively destroyed during insulin-dependent diabetes mellitus, is both a source of IL-1 beta-induced nitric oxide production and also a site of action of this free radical. Pretreatment of beta-cells, purified by FACS with IL-1 beta results in a 40% inhibition of glucose-stimulated insulin secretion that is prevented by the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (NMMA). IL-1 beta induces the formation of nitric oxide by purified beta-cells as evidenced by the accumulation of cGMP, which is blocked by NMMA. IL-1 beta also induces the accumulation of cGMP by the insulinoma cell line Rin-m5F, and both NMMA as well as the protein synthesis inhibitor cycloheximide prevent this cGMP accumulation. Iron-sulfur proteins appear to be intracellular targets of nitric oxide. IL-1 beta induces the formation of an iron-dinitrosyl complex by Rin-m5F cells indicating that nitric oxide mediates the destruction of iron-sulfur clusters of iron containing enzymes. This is further demonstrated by IL-1 beta-induced inhibition of glucose oxidation by purified beta-cells, mitochondrial aconitase activity of dispersed islet cells, and mitochondrial aconitase activity of Rin-m5F cells, all of which are prevented by NMMA. IL-1 beta does not appear to affect FACS-purified alpha-cell metabolic activity or intracellular cGMP levels, suggesting that IL-1 beta does not exert any effect on alpha-cells. These results demonstrate that the islet beta-cell is a source of IL-1 beta-induced nitric oxide production, and that beta-cell mitochondrial iron-sulfur containing enzymes are one site of action of nitric oxide.
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PMID:Interleukin 1 beta induces the formation of nitric oxide by beta-cells purified from rodent islets of Langerhans. Evidence for the beta-cell as a source and site of action of nitric oxide. 133 75

A 15 year old girl with a family history of type 1 multiple endocrine adenomatosis presented with reversible neurological disturbances, hypoglycaemia and hyperinsulinaemia. Initial radiology was normal, but portal venous sampling suggested an insulinoma in the tail of the pancreas which was removed with conservation of the spleen. Hypoglycaemia persisted despite high doses of diazoxide and intravenous dextrose. A second laparotomy revealed a pancreatic endocrine tumour and sub-total pancreatectomy was performed. Histology revealed islet cell microadenomatosis. Hypoglycaemia persisted despite treatment with somatostatin analogues and 40% intravenous dextrose was required to maintain normoglycaemia. A possible lesion near the splenic hilum on computed tomographic scan was reported as a splenunculus although further peripheral, hepatic and portal venous sampling suggested hepatic or systemic lesions. A positron emission scan and selective visceral angiography suggested a lesion in the left upper quadrant. Acute lactic acidosis, rhabdomyolysis and renal failure supervened. Post mortem revealed the putative 'splenunculus' to be a residual insulinoma, whilst the splenic vein was thrombosed, accounting in part for discrepant venous sampling data. Hyperinsulinaemia in type 1 multiple endocrine adenomatosis may require more aggressive surgical and hormonal intervention than when dealing with solitary insulinomas. Insulinomas may mimic developmental abnormalities on computed tomographic scanning.
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PMID:Difficulties in localization and treatment of insulinomas in type 1 multiple endocrine adenomatosis (MEA). 135 Mar 44

Somatostatin-28 (SRIF-28) preferring receptors were solubilized from hamster beta cell insulinoma using the zwitterionic detergent 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate. The binding of the iodinated [Leu8-D-TRP22-Tyr25]SRIF-28 analog (referred to as 125I[LWY] SRIF-28) to the solubilized fraction was time-dependent, saturable, and reversible. Scatchard analysis of equilibrium binding data indicated that the solubilized extract contained two classes of SRIF-28-binding sites: a high affinity site (Kd = 0.3 nM and Bmax = 1 pmol/mg protein) and a low affinity site (Kd = 13 nM and Bmax = 4.7 pmol/mg protein). The binding of 125I[LWY]SRIF-28 to solubilized SRIF-28 receptors was sensitive to the GTP analog guanosine-5'-O-thiotriphosphate, suggesting that receptors are functionally linked to a G-protein. By anion-exchange chromatography of the solubilized extract followed by chromatography on wheat germ agglutinin, a 46-fold purification of SRIF-28 receptors was obtained. At this stage of purification, only high affinity sites were found (Kd = 1 nM) and the GTP effect was not maintained. A specific protein of 37 kDa was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after photoaffinity labeling. We suggest that this protein is the putative SRIF-28 receptor or a subunit thereof.
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PMID:Solubilization and partial purification of somatostatin-28 preferring receptors from hamster pancreatic beta cells. 135 98

A 42-year-old woman with a family history of multiple endocrine neoplasia type 1 (MEN 1) presented with symptomatic hypoglycaemia and peptic ulceration. Investigation revealed an insulinoma, hyperparathyroidism, hypercalcitoninaemia with a positive pentagastrin stimulation test, acromegaly due to a GRF-oma, hyperprolactinaemia and normal serum gastrin levels. Five pancreatic tumours were removed at laparotomy and immunostaining was positive for insulin, calcitonin, somatostatin and glucagon. Post-operatively she developed elevated serum gastrin levels and gross peptic ulceration, despite H2-blockers, and died of gastro-intestinal haemorrhage suggesting that removal of the somatostatinoma may have allowed increased gastrin secretion from a gastrinoma. This case emphasizes the importance of measuring a wide variety of tumour marker peptides in MEN 1 and suggests that caution is required in interpretation of the pentagastrin stimulation test in such cases. Patients with MEN 1 and known peptic ulceration may require perioperative omeprazole treatment even if serum gastrin levels are normal.
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PMID:A case of multiple endocrine neoplasia: hyperparathyroidism, insulinoma, GRF-oma, hypercalcitoninaemia and intractable peptic ulceration. 135 65


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