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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyloid deposits in somatostatinomas are rare observations. To examine the characteristics of this amyloid, we compared amyloid deposits in a somatostatinoma to those found in pancreatic tissue in patients with Type II diabetes mellitus and in insulinomas, using immunohistochemical techniques and specific antibodies to islet amyloid polypeptide or other pancreatic hormones, as well as electron-microscopy. Antibodies to islet amyloid polypeptide regions 8-17 or 25-37 were confirmed to be specific. Amyloid deposits in patients with Type II diabetes mellitus and in insulinomas, but not those in the somatostatinoma strongly reacted with these antibodies, or to an antibody to amyloid P component. Amyloid deposits in the somatostatinoma were not reactive with antibodies to somatostatin or to other pancreatic hormones. Electron-microscopic examinations revealed that amyloid fibrils in the somatostatinoma were thinner and more randomly distributed than were those in islets from patients with Type II diabetes mellitus. As amyloid in somatostatinomas is unlike that consisting of islet amyloid polypeptide or other mature pancreatic hormones, it may be a novel type of local amyloid in pancreatic islets.
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PMID:Amyloid protein in somatostatinoma differs from human islet amyloid polypeptide. 200 Jul 1

Islet amyloid polypeptide (IAPP) in the pancreas of the spontaneously diabetic (BB) Wistar rat was examined by radioimmunoassay, and IAPP mRNA levels were determined by Northern blotting. IAPP-like immunoreactivity in the diabetic rat pancreas was found to be significantly depleted compared with control (non-diabetic) BB rats (85.9 +/- 5 pmol/g in control rats, n = 8, vs 8.97 +/- 0.9 pmol/g in diabetic rats, n = 5; mean +/- S.E.M.). A similar change in insulin concentrations was found, although insulin was present in approximately 100-fold greater amounts than IAPP. Chromatography of the IAPP immunoreactivity revealed a single molecular form, corresponding to synthetic IAPP. Northern blot analysis of pancreatic RNA (n = 4) revealed that IAPP mRNA in the diabetic group was depleted to 22% of the signal intensity in the control group. Insulin mRNA was dramatically reduced to only 4% of the control group and, in contrast, somatostatin was relatively unaffected, with the diabetic group retaining 86% of signal compared with the controls. This animal model of insulin-dependent diabetes results from severe autoimmune destruction of the beta cell. The extremely low levels of both insulin and its messenger RNA are in agreement with this. These results demonstrate that this pathological state is also associated with a loss of IAPP from the pancreas. Insulin-dependent diabetes is associated with a range of metabolic disturbances. It is possible that the concomitant depletion of IAPP may be a contributory factor in exacerbating the condition.
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PMID:Depletion of islet amyloid polypeptide in the spontaneously diabetic (BB) Wistar rat. 201 54

An immunohistochemical study for islet amyloid polypeptide (IAPP) was made on the gastrointestinal (GI) tract and pancreas of man and rat, using antisera raised against a synthetic peptide of C-terminal human IAPP (24-37) and a synthetic peptide of rat IAPP (18-37). A large number of IAPP-immunoreactive cells were found in the pyloric antrum, and a small number in the body of the stomach in both man and rat. Cytoplasmic processes extended out from the bipolar peripheral region of the immunoreactive cells, rather like neuronal processes, and some appeared to make contact with other immunoreactive cells. In addition, small numbers of immunoreactive cells were also seen in the duodenum and rectum, whereas they were absent from the jejunum, ileum and large intestine. An examination was made for evidence of colocalization of IAPP-immunoreactive material with material immunoreactive for gastrin, somatostatin, vasoactive intestinal polypeptide, pancreatic polypeptide, insulin, and glucagon, but none was found. IAPP-immunoreactive cells were also found in the pancreas of non-diabetic and non-insulin-dependent diabetic patients, but they were completely absent from a patient with insulin-dependent diabetes mellitus despite the presence of IAPP in the plasma. The results of these studies suggest that the peptide may have a biological role in situ in the GI tract and, in addition to the pancreas, may be a possible source of plasma IAPP.
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PMID:Islet amyloid polypeptide (IAPP) in the gastrointestinal tract and pancreas of man and rat. 207 50

A novel putative polypeptide hormone identified as islet amyloid polypeptide (IAPP) was recently purified from islet amyloid (IA) of diabetic humans and cats, and also from amyloid of a human insulinoma. Although the function of IAPP is yet unknown, its occurrence in pancreatic endocrine tissue and its partial amino acid sequence identity with calcitonin gene-related peptide (CGRP) suggests an endocrine regulatory effect. In the present investigation, the authors utilized antisera to insulin, glucagon, somatostatin, pancreatic polypeptide, synthetic human CGRP, and a synthetic human IAPP (7-17) undecapeptide to immunohistochemically (PAP technique) document the presence of IAPP immunoreactive cells in the islets of the cat, dog, mouse, and rat, but not in the islets of the horse or calf. In serial sections of islets from these species it was shown that IAPP immunoreactivity occurred in insulin-reactive beta cells. This observation was confirmed immunocytochemically in cat islets by means of protein A-gold probes. With protein A-gold labeling techniques, IAPP immunoreactivity was localized to the outer lucent compartment of the beta cell secretory granule, whereas insulin immunoreactivity was associated with the electron-dense core. These findings provide strong evidence that IAPP or an IAPP precursor is synthesized by beta cells and is stored in beta cell granules for subsequent co-secretion with insulin. The conservation of IAPP in humans and multiple animal species and the localization of IAPP to pancreatic beta cells provide further evidence that IAPP has an important endocrine regulatory function. The propensity of IAPP to polymerize and form IA fibrils in diabetes associated with aging may indicate that IAPP is in some way also linked to the development of Type 2 diabetes.
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PMID:Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques. 327 6

Differential developmental regulation of pancreas-specific genes has not been reported for the human fetal pancreas. We have therefore undertaken a systematic, quantitative analysis of the transcriptional levels of various genes in the human pancreas at different stages of fetal and postnatal development. Using sensitive ribonuclease protection assays, in situ hybridization, and the polymerase chain reaction, our results indicate the following: 1) Transcriptional levels of insulin and amylin remain lower in the fetal than in the adult pancreas, whereas glucagon and somatostatin mRNA levels are consistently greater after 14 wk gestation than postnatally. These results are in agreement with previous immunohistochemical studies of these gene products. 2) The reg gene exhibits a 20-fold increase in mRNA levels after 16 wk gestation. The gene is expressed exclusively in the acinar cells and does not colocalize with insulin. This restricted exocrine expression does not indicate a direct role for the reg gene in islet development. 3) Glucose transporter 2 and glucokinase mRNA are detectable as early as 13 wk gestation and remain low throughout development. Glucose transporter 1 reaches adult transcriptional levels by 18 wk gestation. The early detection of glucose transporter 2 and glucokinase implies that lack of expression of these "glucose sensor" genes does not account for the known insensitivity of the fetal beta-cells to glucose.
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PMID:Developmental gene expression in the human fetal pancreas. 752 96

The mouse homeodomain protein insulin promoter factor-1 (IPF-1) and the rat homologue somatostatin transactivating factor-1 (STF-1) are involved in early pancreatic development and have been implicated in the cell-specific regulation of insulin- and somatostatin-gene expression in mature islet beta- and delta-cells. The cell specificity of IPF-1/STF-1 expression in mature islets is, however, still unclear. Using antisera against recombinant IPF-1 and STF-1 in combination with antisera against islet hormones we find that all beta-cells in monolayers of newborn rat islet cells express STF-1, as do a fraction of the delta-cells. In adult rat and mouse pancreas we find a similar distribution. IPF-1/STF-1 expression was not detected in glucagon-producing alpha-cells. In islet cell tumour models we found that a glucagon/islet amyloid polypeptide (IAPP)-producing pluripotent rat islet cell line (NHI-6F-GLU) expresses STF-1 in all cells prior to insulin gene activation induced by in vivo culture. In contrast, a mouse alpha-cell line (alpha TC1) exclusively expressed IPF-1 in a small subset of insulin-producing cells while an insulin-negative subclone (alpha TC1.9) was negative for IPF-1. In transfection experiments using alpha TC1.9 cells STF-1 activated a rat insulin 1 reporter gene dependent not only on both STF-1-binding sites, but also on the E1-binding site for the helix-loop-helix factor IEF-1. However, the endogenous mouse insulin genes remained inactive in these cells. These results suggest that the insulin promoter acquires its very high, yet cell-specific, activity at least partly through the action of IPF-1/STF-1. This action is dependent on helix-loop-helix factors bound to the E1 element.
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PMID:The homeodomain protein IPF-1/STF-1 is expressed in a subset of islet cells and promotes rat insulin 1 gene expression dependent on an intact E1 helix-loop-helix factor binding site. 757 38

It has already been shown that insulin cells studied under experimental conditions exhibit differences in insulin immunoreactivity and insulin release. The aim of this study, therefore, was to investigate whether insulin cells themselves exhibit morphological abnormalities after transplantation. Insulin cells in rat pancreas isografts with preserved or suppressed exocrine secretion were studied immunocytochemically and ultrastructurally and compared with those of unoperated rats. In isografts with preserved exocrine secretion, cortical insulin cells connected to the exocrine parenchyma or to glucagon or somatostatin cells expressed mostly dense immunoreactivities for insulin and amylin. In addition, medullary insulin cells connected only to other insulin cells displayed faint immunoreactivities for both constituents as found in unoperated animals. After duct ligation, however, pancreatic ducts and elongated capillaries extended into the islets. Corresponding to the stages of islet fragmentation, the heterogeneity among insulin cells underwent changes and was finally abolished. Ultrastructurally, differences in the number of secretory granules paralleled the heterogeneity in insulin immunoreactivity. It is interesting to note that the heterogeneity among insulin cells is preserved after transplantation, indicating that this phenomenon might be of physiological relevance. The heterogeneity may implicate differences in insulin storage and release as found in insulin cells under normal conditions.
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PMID:Insulin cells in rat whole-pancreas isografts display heterogeneous immunoreactivities and ultrastructure. 762 6

Recently five somatostatin receptor subtypes (SSTR) have been cloned, allowing the development of highly specific selective agonists for these SSTR. The present study was undertaken to determine which SSTR is responsible for the inhibitory effect of somatostatin on islet hormone secretion. Single-pass perfusion of four agonists was performed in pancreata obtained from four cadaveric organ donors using a modified Krebs-media with 3.9 mM glucose. Sequential 10-min specific receptor agonist infusions (5 ng/ml) of DC32-87 (SSTR2), DC25-12 (SSTR3), DC32-97 (SSTR3), or DC32-92 (SSTR5) were performed in random order separated by 10-min basal periods. Infusion of SSTR2 agonist into the isolated perfused human pancreas resulted in a significant inhibition of insulin and C-peptide secretion (insulin = -1468 +/- 480 pM, P < 0.05, and C-peptide = -2328 +/- 437 pM, P < 0.05) but not islet amyloid polypeptide or somatostatin. These results suggest that the inhibitory effect of somatostatin on B-cell secretion is mediated through the subtype-2 receptor within the human islet.
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PMID:Somatostatin inhibits B-cell secretion via a subtype-2 somatostatin receptor in the isolated perfused human pancreas. 763 Jan 42

A number of cell and tissue-specific differences have been described in studies of the regulation of glucagon gene expression. DNA sequences important for islet cell-specific transcription are not sufficient for expression of the glucagon gene in the intestine, and the posttranslational processing of proglucagon results in the liberation of different peptides in pancreas and intestine. We have studied the control of glucagon gene expression in STC-1 cells, a mouse intestinal neuroendocrine cell line. STC-1 cells are plurihormonal and contain glucagon, somatostatin, amylin, and cholecystokinin, but not insulin mRNA transcripts. Glucagon gene expression is regulated by a cAMP-dependent pathway in STC-1 cells, with an increase in glucagon mRNA transcripts detected 2 h after forskolin stimulation. The levels of glucagon mRNA transcripts remained elevated for 36-48 h after forskolin stimulation, but cycloheximide inhibited the forskolin induction of glucagon gene expression. Although sequences up-stream of -1300 are necessary for intestine-specific glucagon gene transcription in transgenic mice, glucagon-chloramphenicol acetyltransferase (CAT) plasmids containing less than 1300 basepairs of 5'-flanking sequences were transcriptionally active in STC-1 cells. The transcriptional properties of specific DNA elements important for glucagon gene transcription in islet cells differed in STC-1 cells. Deletion of the islet cell-specific enhancer G3 element resulted in an increase in the transcriptional activity of transfected glucagon-CAT plasmids, suggesting that G3 may function as a negative element in STC-1 cells. Deletion of the cAMP response element sequence from -291 to -298 did not eliminate the forskolin induction of glucagon-CAT activity in STC-1 cells, and forskolin responsiveness was maintained with deletions containing only 60 basepairs of rat glucagon gene 5'-flanking sequences. The results of these experiments define novel functional properties for previously characterized domains within the rat glucagon gene 5'-flanking region, suggesting that mouse STC-1 cells may be a useful cell line for studies of the molecular control of glucagon gene expression.
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PMID:Multiple cis-acting domains mediate basal and adenosine 3',5'-monophosphate-dependent glucagon gene transcription in a mouse neuroendocrine cell line. 767 66

Studies were undertaken to elucidate further the mechanism whereby the pancreatic peptide amylin induces insulin resistance. Sixteen male Sprague-Dawley rats underwent hyperinsulinemic (14 pmol/kg/min, 0 to 120 minutes) euglycemic clamps in the presence or absence of amylin (500 pmol/kg/min, 60 to 120 minutes). Amylin induced insulin resistance at both the hepatic level (mean +/- SE: hepatic glucose output [HGO] with amylin 1.4 +/- 0.2 v without amylin -1.9 +/- 0.3 mmol/kg/h, P < .001) and peripheral level (glucose disposal [Rd] with amylin 5.0 +/- 0.2 v without amylin 8.5 +/- 0.6 mmol/kg/h, P < .001). Serum insulin levels were similar in the presence or absence of amylin alone (661 +/- 89 v 636 +/- 50 pmol/L, respectively, P = NS), but were significantly less when somatostatin (SRIF) was simultaneously infused (408 +/- 15 pmol/L, P < .02 v the other two groups). This suggests that endogenous insulin production was not suppressed by amylin under these study conditions. Similar findings were obtained in 18 animals in the absence of exogenous insulin infusion. In vitro kinase activity toward histone of skeletal muscle insulin receptors (IRs) activated by insulin in vivo was reduced in the presence of amylin to 6.0 +/- 0.8 versus 9.1 +/- 1.2 fmol phosphate into histone (insulin-infused) and 3.9 +/- 0.7 versus 6.9 +/- 1.4 (non-insulin-infused; P < .03 by ANOVA). Serum calcium was significantly decreased in amylin-treated animals (1.93 +/- 0.04 v 2.30 +/- 0.05 mmol/L, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amylin-mediated reduction in insulin sensitivity corresponds to reduced insulin receptor kinase activity in the rat in vivo. 778 53


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