Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vicinity of several hormone-producing glands as part of the anatomy of the intestinal tract and the resulting interaction has been confirmed by the discovery of hormonal factors of a specifically gastro-intestinal origin. Today we are mainly interested in the interaction between intermediary metabolism and incretory intestinal function; this is characterized by the joint action of conventional glandular hormones such as insulin and pancreatic glucagon as well as by the incretion of diffuse intestinal organs, hormones such as secretin, pancreozymin, motilin, VIP and GIP. The latter are at present subject of active research with the object of discovering their physiological significance be it as tissue hormones or as humoral agents with a "long distance" impact; their role within pathophysiology is also of interest. GIP ("gastric inhibitory peptide"), apart form acting upon the intestinal tract, also causes a marked rise in insulin production; this GIP possibly is the factor responsible for the difference in glucose tolerance following i. v. or oral administration of glucose, something that scientists have been trying to discover for a long time. We have also endeavored to investigate somatostatin. This substance was originally discovered as a hypothalamic factor with inhibitory action on growth hormone secretion; in the meantime, however, cells containing and possibly also producing somatostatin have also been detected in the intestine and particularly in the islets of Langerhans (D-cells). Since somatostatin inhibits insulin secretion and especially glucagon release as well as the exretory functions of the stomach and of the pancreas, the significance of this hormone possibly is that of a tissue hormone with inhibitory action on adjacent cells. As factor inhibiting both endocrine and exocrine secretory processes it would combine these two complexes. The possible therapeutic significance of somatostatin administration to diabetics would lie in the saving of insulin. A third sector of present-day research deals with the interaction between the calcium metabolism and the hormones involved as well as the intestine. We know that patients suffering from primary hyperparathyroidism are prone to contract stomach ulcers and pancreatitis; patients with a gastrinoma and a hyperfunction of the epithelial bodies suffer from a Zollinger-Ellison-sindrome and this again suggests association with endocrine polyadenomatosis (Wermer syndrome). The inhibitory action of the parathormone antagonist calcitonin on the exocrine functions of the intestinal tract, such as the acid secretion of the stomach and the enzyme secretion of the pancreas, have already given rise to some considerations and experiments relative to treatment. It is to be hoped that because of all the joint observations cited above there will be better intergration of research both from the aspect of gastro-enterology and endocrinology. This might hopefully elucidate some of the unresolved problems ranging from basic research to practical application.
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PMID:[Interaction between gastrointestinal hormones and endocrine regulation]. 0 83

Several gastrointestinal peptides with proven or suggested endocrine or paracrine functions influence gastric acid secretion, gastrointestinal motility, and mucosal blood flow. Increased or decreased release of such factors could participate in the pathogenesis of duodenal ulcer disease by inducing increased gastric acid concentration in the duodenal bulb. To date, increased stimulation of parietal cells by gastrin has been demonstrated only in patients with gastrinoma, G-cell hyperplasia, gastric outlet obstruction, hyperparathyroidism, excluded antrum, and short bowel syndrome, but not in the usual duodenal ulcer disease. Also, a defective inhibition of parietal cell function by endocrine or paracrine factors, such as gastric inhibitory polypeptide, secretin, somatostatin and vasoactive intestinal polypeptide, seems not to exist in patients with duodenal ulcer disease. However, as long as the physiology of gastrointestinal peptides in gastric secretion and motility is not understood, a possible role of these factors in the pathogenesis of simple duodenal ulcer disease cannot be excluded.
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PMID:Endocrinology of duodenal ulcer. 51 78

The authors report the case of a 48 years old man presenting a pancreatic islet cell carcinoma (gastrinoma) with liver, nodes and peritoneal metastases, associated with an elevated alpha-fetoprotein (AFP) concentration. Incomplete remission was first obtained with a chemotherapy using Streptozotocin combined with 5-Fluorouracil, in association with a Somatostatin analogue (SMS 201-995). But when relapses occur, another chemotherapy was not so effective. Serum gastrin and AFP levels had the same evolution and appear to have the same interest to follow the course of the disease.
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PMID:[Pancreatic endocrine tumor with metastases and increase of alpha-fetoprotein. A case report]. 128 58

The significance of the enterochromaffin-like (ECL) cell as a critical endocrine regulator of gastric fundic mucosal function has only recently been recognized. Although the percentage of these cells present in the human fundic mucosa is less than that in rodents, the observation that they secrete histamine and are probably important modulators of parietal cell function has resulted in their attaining some considerable biological significance. The further identification of gastrin and somatostatin receptors on the surface of the ECL cells has suggested that other neurohormonal influences may be significant in the regulation of parietal cell function, utilizing the ECL cell as an intermediate modifier. While abnormalities of ECL cells in the human stomach (hyperplasia/neoplasia) have been mostly confined to observations in patients with pernicious anemia and atrophic gastritis, the recent recognition of hyperplasia in pharmacotherapeutically induced achlorhydric or hypochlorhydric states has excited considerable interest. It has been proposed that the generation of luminal hypo- or achlorhydria by powerful acid inhibitory pharmacotherapy may result in hypergastrinemia. This condition is responsible initially for the development of hyperplasia and, subsequently, possibly even neoplasia of the ECL system of the fundic mucosa. This phenomenon seems to be prevalent in rodents but has so far been only rarely observed in humans, e.g., pernicious anemia, atrophic gastritis. In particular, patients with the gastrinoma component of the multiple endocrine neoplasia type I syndrome exhibit ECL-cell hyperplasia and neoplasia after exposure to acid inhibitory pharmacotherapy. It is therefore likely that an underlying genomic phenomenon is necessary prior to the induction of hyperplasia and subsequent neoplastic transformation. The scientific evaluation of the relationship between gastrin, ECL-cell function, and the development of hyperplasia and neoplasia may provide some important information in regard to the molecular evolution of gastrointestinal neuroendocrine disease states. It is possible that the future pharmacotherapy of acid secretory disease may require regulation not only of parietal cell but of ECL-cell function.
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PMID:The pathobiology of the human enterochromaffin-like cell. 134 Oct 78

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

A total of 24 patients with endocrine neoplasms of the pancreas were clinicopathologically and immunohistochemically studied. They consisted of 18 patients with adenoma and 6 with carcinoma. Of the 24 patients, 13 developed attacks of hypoglycemia due to hyperinsulinemia, and 1 developed an uncontrollable duodenal ulcer caused by the hypersecretion of gastrin, however, the remaining 10 were asymptomatic. No prediction could be made as to the site of origin of the tumors. A clear difference was seen between adenoma and carcinoma in the size of the mass, the mean greatest diameter of the 18 adenoma cases being 1.7 cm, while that of the 6 carcinoma cases was 7.3 cm. One of the 13 insulinomas and a gastrinoma was malignant, while all 24 tumors were positive for neuron-specific enolase. The 13 insulinomas were diffusely positive for insulin and 5 were also shown to be focally immunoreactive for gastrin, with 3 also being immunoreactive for somatostatin and 2 for pancreatic polypeptide. The gastrinoma showed immunoreactivity for somatostatin, insulin, pancreatic polypeptide, and glucagon in addition to a positivity to gastrin. The above findings thus indicate the multiple hormone synthesis of endocrine neoplasms of the pancreas.
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PMID:Endocrine neoplasms of the pancreas: a clinicopathologic study of 24 cases and immunohistochemical remarks. 139 40

The therapeutic principles in the management of endocrine gastroenteropancreatic (GEP) tumours include surgical extirpation of the primary tumour in the absence of metastases and medical control of symptoms in the preoperative phase. In the presence of metastases only palliative procedures are available. Tumour growth might be controlled by surgical procedures as debulking of tumour masses, medically by chemotherapy and more recently by new developments as a long-acting somatostatin analogue (SMS 201-995) and alpha-interferon. Their efficacy is currently evaluated in prospective studies. In contrast to inhibition of growth symptoms derived from excessive hormone production by GEP tumours can be well controlled. SMS 201-995 effectively prevents or at least improves flush and diarrhoea in the carcinoid syndrome, disabling diarrhoea in the Verner-Morrison syndrome and migratory erythema in the glucagonoma syndrome. SMS acts by inhibition of hormone release from the tumour and by a direct mechanism at the site of the target cell via SMS receptors present on tumour and target cells. For control of acid hypersecretion in gastrinoma patients omeprazole is superior to all former and present alternatives and replaced total gastrectomy completely. A similarly effective drug to prevent hypoglycaemia due to uncontrolled insulin release from insulinomas is not available since neither SMS nor diazoxide are effective in every insulinoma patient.
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PMID:Therapeutic strategies in the management of endocrine GEP tumours. 170 88

Because of its widespread distribution within the nervous system and the gastro-enteropancreatic (GEP) system and its diverse physiological inhibitory actions on various gastrointestinal functions, including endocrine and exocrine secretion, motility, liver and splanchnic blood flow and absorption, native somatostatin has been viewed as a possible therapy for many diseases. However, its short duration of action and consequent limited clinical usefulness have been overcome with the availability of Sandostatin, a long-acting, synthetic octapeptide analogue of the naturally occurring hormone. Sandostatin represents a significant advance in the treatment of GH and TSH secreting pituitary tumours and GEP endocrine tumours (carcinoid tumour, VIPoma, glucagonoma, insulinoma, and gastrinoma). Preclinical in vitro and animal studies have shown the antineoplastic activity of the compound. Moreover, because of a possible direct effect on somatostatin receptor-positive endocrine tumour cells and indirect effect whereby Sandostatin lowers GH, IGF-1 and numerous gastrointestinal peptides, Sandostatin may prove useful as an adjunctive therapy in cancer patients. In vivo labelling of somatostatin receptor-positive tumours with radiolabelled somatostatin analogues now allows localisation of such tumours and their metastases. Moreover, targeted irradiation of these tumours by beta particle emitting isotopes attached to such somatostatin analogues may become possible. The use of Sandostatin in acute oesophageal variceal bleeding, pancreatic pseudocysts, gastrointestinal and pancreatic external fistulae, short bowel syndrome, dumping syndrome and AIDS-related refractory hypersecretory diarrhea has provided encouraging results. Preliminary reports indicate efficacy of Sandostatin in psoriasis, autonomic neuropathy (postprandial and orthostatic hypotension) and its ability to reduce height velocity in tall adolescents. The ultimate role of Sandostatin as a therapeutic agent in these disorders is being explored in prospective clinical trials.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Future medical prospects for Sandostatin. 198 Jul 78

A potent and long-acting somatostatin analogue, SMS 201-995 (SMS) is currently employed for the treatment of various diseases with hypersecretion of hormones such as acromegaly and gastrinoma. The suppressive effects of SMS are also reported on the other pituitary and gastrointestinal hormones. The corticotropic-adrenocortical axis is a crucial hormonal complex in maintaining normal activity and life itself. In this study, the effects of SMS on corticotropic-adrenocortical functions were studied, since the effects of SMS on this hormonal axis are not well established. Seven normal males received a sc injection of 100 micrograms SMS or placebo at 0830 h and 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) intravenously (SMS-hCRH study). Five of the 7 subjects were given an injection of a synthetic (1-24) ACTH (250 micrograms or 63 micrograms) at 0900 h after 100 micrograms SMS or a placebo at 0830 h (SMS-ACTH study). Blood samples were drawn at -30, 0, 15, 30, 60, 90 and 120 min after the hCRH injection for the determination of ACTH and cortisol in the SMS-hCRH study, and cortisol and aldosterone in the SMS-ACTH study. Although significant rises in plasma ACTH and cortisol levels were observed regardless of the preinjection of SMS, their responses to hCRH were significantly lower with the pretreatment with SMS than without SMS. A significant increase in plasma cortisol and aldosterone was observed in response to synthetic ACTH with both ACTH alone and the combined administration of SMS and ACTH, at either dose of ACTH. However, no significant difference in cortisol and aldosterone secretion was detected with and without SMS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of a long-acting somatostatin analogue on pituitary-adrenocortical secretion in normal human subjects. 216 54

Somatostatin (SS) receptor status was investigated in the tumor tissues from 62 patients with carcinoid tumors and 15 patients with islet cell carcinomas using receptor autoradiography techniques with two different iodinated somatostatin analogues as radioligands, a [Leu8, DTrp22, Tyr25]somatostatin-28 and a somatostatin octapeptide, Tyr3-octreotide. The carcinoid tumors were either primaries (n = 32) or metastases (n = 43), sampled as surgical specimens or as small needle liver biopsies. Fifty-four of 62 carcinoid patients had SS receptor-positive tumors (87%). All 15 islet cell carcinoma patients had positive tumors (4 primaries, 11 metastases), i.e., 3 vipomas, 3 insulinomas, 2 glucagonomas, 1 gastrinoma, 2 polyfunctional tumors, and 4 nonfunctioning tumors. Saturation and competition experiments on tissue sections revealed saturable, high affinity binding sites pharmacologically specific for bioactive SS analogues. In a majority of the tumors, the receptors were densely distributed and were always homogeneously found in the whole tumor. All except two tumors were labeled with both radioligands. Multiple liver metastases (n = 16) from three different patients were all shown to contain a comparable amount of receptors. SS receptors could be demonstrated even in very small tissue samples of liver metastases obtained by percutaneous liver biopsies (mean weight, 6.8 mg). The majority of the eight SS receptor-negative carcinoids were mainly bronchial carcinoids (n = 5), usually poorly differentiated. On the contrary, SS receptor-positive cases were never found to be anaplastic. All tumors except one from patients pretreated with octreotide (3 days to 3.8 years) were SS receptor positive. In the majority of carcinoids or islet cell carcinomas, the SS receptor status correlated with the in vivo biochemical response (hormone inhibition) to octreotide. These data demonstrate (a) the high prevalence of SS receptors in the primary tumors of both carcinoids and islet cell carcinomas, (b) their presence in metastases as well, (c) their continuous expression even during long term octreotide therapy, (d) the possibility of measuring SS receptors in percutaneous needle liver biopsies, and (e) the evidence of their functionality. This study therefore suggests that tumoral SS receptors may be the likely molecular basis for octreotide action and may be an important parameter for predicting the therapeutic efficacy of SS analogues in carcinoids and islet cell carcinomas.
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PMID:Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. 216 86


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