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)

Somatostatin and its analogue SMS 201-995 inhibit high voltage-activated (HVA) Ca2+ currents in the rat insulinoma cell line RINm5F which stably express cloned human somatostatin receptor subtype 2 (hSSTR2). In contrast, neither somatostatin nor SMS 201-995 suppresses the HVA Ca2+ currents in RINm5F which stably express cloned hSSTR1. These results suggest that somatostatin-induced inhibition of HVA Ca2+ currents is mediated by a specific receptor subtype and that inhibition of calcium influx through HVA Ca2+ channels is one of the mechanisms of SMS 201-995 action on inhibitory processes of hormone secretion and cell proliferation.
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PMID:Somatostatin receptor subtype SSTR2 mediates the inhibition of high-voltage-activated calcium channels by somatostatin and its analogue SMS 201-995. 798 82

The localization of islet cell tumours presents a challenge to the radiologist and requires meticulous attention to detail in both technique and interpretation. As several imaging techniques are capable of demonstrating the tumour and none is absolutely accurate, a rational approach to the localization of these tumours requires a careful consideration of cost, sensitivity and the availability of special expertise. In almost all cases, initial imaging is performed with a combination of transabdominal ultrasound and CT. This will demonstrate the tumour and any hepatic metastases in about 40% of gastrinomas, 80% of insulinomas and almost all other functioning and non-functioning tumours. Where these tests are negative or equivocal, arteriography (which may be combined with ASVS) is the next line of investigation. If the tumour remains undetected, it is likely to be a small insulinoma or gastrinoma. Further investigation is dependent on local practice and the tumour type. Endoscopic ultrasound is rapidly emerging as a technique of high sensitivity in detecting small pancreatic tumours and may also demonstrate extrapancreatic gastrinomas. Transhepatic venous sampling and somatostatin receptor imaging have the advantage that they are not directly dependent on tumour size and they are particularly applicable to difficult cases where other imaging modalities are negative. TPVS is invasive and, while sensitive for insulinomas, is frequently unhelpful in gastrinomas. Somatostatin receptor scintigraphy, on the other hand, is more sensitive for gastrinomas. In future, MRI may prove to be at least as accurate as CT but as yet its exact role is uncertain. At the time of surgery, intraoperative ultrasound is a useful adjunct to palpation, and may avoid a standard distal pancreatectomy in patients with insulinoma.
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PMID:Imaging islet cell tumours. 801 89

We investigated the 24-hour mean blood glucose and serum insulin (IRI), C peptide (C pep) and glucagon concentrations before (pre) and after (post) continued treatment with octreotide (100 mcg three time daily by s.c. injection) in a woman, 68 years old, affected by a nine years long benign insulinoma. The blood pool to dose 24-hour mean glucose and all hormone concentrations was obtained by equal quantities of blood samples taken every 2-hour over 24-hour. The IRI, C pep, glucagon, glucose circadian pattern and IRI/glucose ratio were determined on remaining blood portions. After continued treatment with octreotide was significantly reduced the exaggerated and inappropriate insulin (pre = 77.08 +/- 23.6 microUI/ml; post = 15.19 +/- 2.3 microUI/ml; p < 0.001) and C pep secretion (pre = 4.17 +/- 0.4 ng/ml; post--1.64 +/- 0.04; p < 0.001), while the blood glucose levels were significantly elevated (pre = 40.46 +/- 3.1 mg/dl; post = 132.46 +/- 6.9 mg/dl; p < 0.001). Also glucagon levels were significantly inhibited (pre = 73.53 +/- 12.19 pg/ml; post = 46.80 +/- 9.1 pg/ml; p < 0.05). The long-acting somatostatin analogue has improved a lot IRI/glucose ratio (pre = 1.9 +/- 0.4; post = 0.12 +/- 0.04; p < 0.001). A significant positive correlation was found between IRI and C pep before (r = 0.93; p < 0.001) as well after octreotide treatment (r = 0.85; p < 0.001). A significant positive correlation (r = 0.69; p < 0.008) between IRI and glucose was observed only after octreotide treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Benign insulinoma. Efficacy of preoperative treatment for persistent hyperinsulinemia using a synthetic somatostatin analog]. 803 68

The difficult and controversial diagnostic and therapeutic management of patients having gastrinoma or insulinoma with multiple endocrine neoplasia type I (MEN-I) has been discussed by reference to the literature and a personal series of 45 gastrinoma/MEN-I patients followed consecutively at Bichat Hospital. In both gastrinoma/ and insulinoma/MEN-I patients, anatomic distribution and morphology of tumoral process(es) are usually multiple, diffuse, of small size, and associated with endocrine cell hyperplasia and even nesidioblastosis. These features enhance the difficulty of tumor localization and eradication. Despite the dramatic development of modern medical imagery and surgical experience, the real possibility, on a long-term basis, of curing the patients from their disease remains limited, especially in the gastrinoma/MEN-I patients. In the latter group, according to our experience, persistence or recurrence of the disease after surgery is usual, and metachronous hepatic metastasis development is frequently observed when the follow-up is long enough. Patients with liver metastases, however, seem to undergo a more indolent course than sporadic gastrinoma cases. In insulinoma/MEN-I patients, removal of the functionally dominant islet cell area(s) is essential. Various preoperative and intraoperative localization techniques allow efficacious selective pancreatic surgery in many cases. The latter refinements and the promises of long-acting somatostatin analogs, if confirmed, might restrict to exceptional circumstances the indication of near-total or total pancreatectomy.
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PMID:Current approach to the management of gastrinoma and insulinoma in adults with multiple endocrine neoplasia type I. 810 51

The presence of somatostatin receptors has been demonstrated in various endocrine tumors as well as in normal tissues. We recently have cloned five human somatostatin receptor subtypes (SSTR1-SSTR5). These mRNAs are expressed in a tissue-specific manner. In this study, we have determined the somatostatin receptor subtypes expressed in various endocrine tumors using a reverse transcriptase polymerase chain reaction method. In two cases of glucagonoma and its metastatic lymph nodes in one case, all the SSTR subtype mRNAs except SSTR5 mRNA were expressed. In four cases of insulinoma, SSTR1 and SSTR4 mRNAs were detected, but SSTR2 mRNA was not detected in one case and SSTR3 mRNA was not detected in two cases, indicating a heterogeneous expression of SSTR subtypes in insulinomas. Interestingly, SSTR3 mRNA, which is highly expressed in rat pancreatic islets, is not expressed in normal human pancreatic islets, while SSTR1, SSTR2, and SSTR4 mRNAs are expressed. In three cases of pheochromocytoma, SSTR1 and SSTR2 mRNAs were detected, showing an expression pattern identical to that of normal adrenal gland. In a carcinoid, SSTR1 and SSTR4 mRNAs were detected. We have also found that human SSTR2 shows a high affinity for SMS 201-995, which has been used clinically for the treatment of endocrine tumors. Since SMS 201-995 was effective in the treatment of a patient with glucagonoma in which SSTR2 mRNA was present, but had no effect in a patient with carcinoid in which SSTR2 mRNA was not detected, this study suggests that the efficacy of SMS 201-995 may depend, at least in part, on the expression of SSTR2 in tumors.
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PMID:Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors. 813 73

The clinical investigations carried out in a 58 years woman complaining of malaise led to the discovery of an hypoglycaemia resulting from a secreting pancreatic insulinoma. In addition, a chronic pancreatitis, an endocrine hyperplasia (possible nesidioblastosis) and a villous adenomatosis of the pancreatic duct were diagnosed on two biopsies. The immunohistological tests performed on the insulinoma showed insulin, calcitonin and gastrin labelled cells. Electron microscopy displayed numerous neurosecretory granules. The peritumoral endocrine hyperplasia contained intermingled B, A and D cells respectively labelled by insulin, glucagon and somatostatin. Following the operation, the patient recovered without recurrence of the hypoglycaemia (three year follow-up). Factors which may explain such a rare pathological association are discussed.
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PMID:[Pancreatic insulinoma, adenomatosis of the Wirsung's duct and chronic pancreatitis. Apropos of a case]. 813 87

In-111 DTPA octreotide, a labeled somatostatin analog, was reported to be superior to I-123 octreotide for detection of somatostatin-receptor-bearing tumors because of longer half-life and better labeling characteristics. In addition, renal rather than hepatobiliary clearance decreases intestinal interference and greatly reduces accumulation of the tracer in the gallbladder. Using the In-111 labeled octreotide, the authors noted distinct gallbladder visualization in one patient with an insulinoma who was studied following an overnight fast. In two additional patients scanned in the fasting state gallbladder uptake was also demonstrated. In all 3 patients, this uptake disappeared following a meal. The authors conclude that when using this imaging modality, abdominal scans should not be performed in the fasting state. Furthermore, if significant uptake is demonstrated in the gallbladder area, imaging should be repeated several hours later, following a fatty meal. Both false-positive and false-negative findings of pathologic uptake in this area will thus be avoided.
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PMID:Gallbladder visualization with In-111 labeled octreotide. 818 97

Mice carrying a Moloney murine sarcoma virus-(MSV) simian virus 40 large T transgene develop heritable tumors including endocrine pancreatic tumors. We have established several independent transgenic mouse lines expressing this transgene. One of these lines, designated MSV125, is characterized by the development of congenital cataracts and either pancreatic or brain tumors. The development and histopathology of the pancreatic tumors were studied by light microscopy and immunocytochemistry for large T antigen, neuron-specific enolase, insulin, proinsulin, glucagon, somatostatin, pancreatic polypeptide, gastrin, and serotonin. The 23 tumors examined were similar to human endocrine pancreatic tumors with respect to their macroscopic and histological features. We classified 91% of the tumors as insulinomas based on the predominance of insulin immunoreactivity. In newborn and young transgenic animals, nesidioblastosis and islet cell proliferation, consisting mostly of insulin containing beta cells, was obvious and persisted into adulthood. In transgenic animals more than 2 months old, islet hyperplasia and dysplasia predominated from which single tumors developed. Hyperplastic and dysplastic islets were composed mostly of beta cells. Large T antigen was detectable not only in tumor cells, but also in cells of normal and hyperplastic islets and in islet anlagen of newborn transgenic mice, indicating expression of the transgene in the endocrine part of the pancreas. Large T antigen-immunoreactivity was restricted to the beta cells. Insulinomas of the MSV-simian virus 40 T antigen-derived MSV125 transgenic mouse line may represent a valuable model for the study of the development and biology of insulinoma.
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PMID:Endocrine pancreatic tumors in MSV-SV40 large T transgenic mice. 838 73

Gut tumor syndromes are rare, occurring in less than two cases per million population per year: Insulinomas are most common and gastrinomas are less common; all the others are extremely rare. Conventional treatment of the symptoms caused by these tumors has included surgery, hepatic arterial embolization, and chemotherapy; some patients with Zollinger-Ellison syndrome (ZES) have been treated with specific agents such as gastric antisecretory drugs. The development of octreotide, a synthetic, long-acting analogue of the natural peptide somatostatin, has offered an alternative to such therapies. Octreotide has a half life of > 100 minutes and inhibits both physiological- and tumor release of many peptides. It also has direct effects on the gut that modify secretion and motility. Octreotide has been shown to be particularly useful for the symptoms of tumors producing vasoactive intestinal peptide (VIP), and of the carcinoid syndrome. It is also useful in patients with glucagonomas, with growth hormone-releasing hormone producing tumors, and in some patients with Cushing's syndrome and unresectable insulinomas. Octreotide is effective in patients with ZES, but alternative therapies such as omeprazole are more effective, safer, and more convenient for those patients. Side effects of octreotide have not been troublesome in these patients, but the incidence of long term effects is still not entirely clear. Octreotide has proved to be a significant advance in the treatment of patients with islet cell tumors.
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PMID:Use of octreotide acetate for control of symptoms in patients with islet cell tumors. 839 51

The results of octreotide scintigraphy, performed in two patients with malignant endocrine pancreatic tumors, were compared with the effect of somatostatin-14 and its analogue octreotide on hormonal levels and clinical outcome. Radiolabeled octreotide failed to demonstrate any tumor localisation in a patient with a malignant insulinoma. Nevertheless, IV injection of somatostatin and octreotide resulted in a significant decrease in peripheral insulin levels. Moreover in this patient, chronic treatment with a high dose of octreotide subcutaneously was able to transiently lower the incidence of hypoglycemic events. In a second patient with metastatic PP-oma, 111In-octreotide disclosed a pancreatic tumor in the tail of the pancreas and metastatic supraclavicular lymph nodes. In this patient IV administration of somatostatin and octreotide inhibited the hormonal secretion of the tumor but subcutaneous injection of octreotide induced hardly any decrease in plasma PP levels and failed to affect tumor growth. These observations find a possible reason for this in the heterogeneous affinity of the somatostatin receptors in endocrine pancreatic tumors. They indicate that octreotide scintigraphy alone should not be used to select patients with neuroendocrine tumors who can benefit from chronic treatment with the somatostatin analogue.
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PMID:111In-octreotide scintigraphy: a tool to select patients with endocrine pancreatic tumors for octreotide treatment? 853 89


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