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)

Circulating levels of insulin, proinsulin-like component, glucagon, growth hormone, and pancreatic polypeptide were measured in 12 patients with functioning insulinomas, and the suppressibility of serum insulin by somatostatin and diazoxide was assessed before surgical removal of the tumors. The hormone content of the tumors was evaluated by radioimmunoassay and by immunofluorescence and the structure of the tumor cells by electron microscopy. Based on these findings, we propose a new classification of insulinomas in two groups: group A is characterized morphologically by abundant well-granulated typical B-cells, trabecular arrangement of tumor cells, and uniform insulin immunofluorescence; functionally, these tumors are associated with a moderate elevation of proinsulin-like component and with an almost complete suppressibility of serum insulin by somatostatin and diazoxide. In contrast, tumors of group B are characterized by scarce well-granulated typical B-cells, a medullary-type histologic structure, and irregular insulin immunofluorescence; functionally these tumors show elevated circulating levels of proinsulin-like component and a marked resistance of insulin secretion to somatostatin and diazoxide inhibition. This way of separating human insulinomas in groups A and B represents a simplification of existing classifications and emphasizes the quantitative ultrastructure in relationship to suppressibility of insulin secretion. The proposed classification of human insulinomas in groups A and B, however, does not allow the assessment of the clinical or histopathologic malignancy of the tumors.
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PMID:Functional and morphologic characterization of human insulinomas. 631 53

It is well known that there are functional and morphological similarities between the salivary glands and the pancreas. Amylase, kallikrein and glucagon are present in both tissues. Morphological similarities of the two tissues have been observed by using a light and electron microscope. In order to examine the pathophysiological relationship between the pancreas and the salivary glands, an immunohistochemical study using antisera against proline-rich peptide P-C, which was recently isolated from human whole saliva, was carried out on the human salivary glands and the pancreas. Peptide P-C like immunoreactivity was found not only in the salivary glands but also in the pancreatic islets. Furthermore, observation of serial thin sections immunostained with insulin, glucagon, somatostatin, PP antisera and antisera against peptide P-C revealed that peptide P-C like immunoreactivity-containing cells were identical to insulin containing B-cells. As the antisera against peptide P-C did not have any cross-reactivity to other kinds of peptide including insulin, glucagon, somatostatin, pp, VIP, human C-peptide and kallikrein, the present finding suggests that peptide P-C like immunoreactivity is present in the B-cells independently of insulin and proinsulin. The finding seems to be a new addition to the lists of proof which support the presence of a pathophysiological relation between the salivary glands and the pancreas. Although it seems likely that peptide P-C like immunoreactivity in the pancreatic B-cells may play some role in the function of the B-cells, since this material was present only in the B-cells among four kinds of cells in the pancreatic islets, its exact pathophysiological role remains to be elucidated.
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PMID:[The presence of proline-rich peptide P-C like immunoreactivity in the human pancreatic B-cells]. 634 34

A 12.5-kilodalton protein not related to insulin or glucagon was detected in pulse-chase-labeled rat islets of Langerhans. Although this protein reacted poorly with various somatostatin antisera, analysis of two-dimensional peptide maps showed that it contains all of the tryptic fragments of somatostatin, which is located at its COOH terminus. Proteolytic conversion of the putative prosomatostatin, which took place parallel to the processing of proinsulin and proglucagon in pulse-chase experiments, coincided with the appearance of newly synthesized somatostatin and proceeded without the apparent involvement of major intermediate forms.
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PMID:Identification of prosomatostatin in pancreatic islets. 677 54

The sera of 30 patients who had been treated with conventional beef insulin were tested for binding of insulin and other pancreatic hormones. All showed antibody binding of insulin, 29 binding of proinsulin, 29 binding of pancreatic polypeptide, two binding of glucagon but none of the sera bound vasoactive intestinal peptide or somatostatin. After changing therapy to highly purified pork insulin the binding capacity of sera for insulin and the other hormones was monitored for up to 35 months and a steady fall was found in nearly all cases. In eight of the patients conventional beef insulin treatment was resumed: in one month binding of insulin and of the other hormones increased back to the initial levels. In eighteen subjects who had only received highly purified pork insulin low levels of insulin binding were found with no binding of proinsulin or other hormones. The amounts of proinsulin and contaminating hormones in highly purified pork insulin are so low that they are not immunogenic; conventional beef insulin not only contains immunogenic amounts of proinsulin and the contaminating hormones pancreatic polypeptide and glucagon but also is more immunogenic than purified pork insulin.
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PMID:Decrease of antibodies to insulin, proinsulin and contaminating hormones after changing treatment from conventional beef to purified pork insulin. 698 74

We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF-II (molecular weight 11 kDa) which probably represents a non-glycated form of pro-IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently described unextracted assay directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct plasma estimation (plasma E-21) of larger molecular forms of IGF-II without interference from normal IGF-II and IGF binding proteins. Basal values were grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM) before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change in plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained normal and IGF-I increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A case of hepatoma associated with hypoglycaemia and overproduction of IGF-II (E-21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin. 752 21

An extract of a neuroendocrine tumor of the human pancreas contained a high concentration of insulin and the C-peptide of proinsulin, as determined by radioimmunoassay, together with somatostatin, calcitonin, and thymosin beta 4. Analysis of the molecular forms of the proinsulin-derived peptides by high-performance liquid chromatography demonstrated that insulin was stored in the tumor as the intact peptide. In contrast, metabolites of C-peptide, representing the (1-21), (1-23), (1-25) and (1-29) N-terminal fragments, were isolated from the extract in addition to intact C-peptide. Generation of these metabolites involves cleavage of Xaa-Leu or Leu-Xaa bonds. Previous immunohistochemical studies have identified cathepsin B in secretory granules and lysosomes of human insulinoma cells. Synthetic human C-peptide was rapidly cleaved by purified human cathepsin B, primarily at the site of leucine residues, to give several metabolites, including the (1-25) and (1-23) fragments. The data indicate that the C-peptide of proinsulin is selectively metabolized in the neoplastic B cell by a mechanism that involves proteolytic cleavages in the C-terminal region of the peptide.
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PMID:Intracellular degradation of the C-peptide of proinsulin, in a human insulinoma: identification of sites of cleavage and evidence for a role for cathepsin B. 771 41

The expression of the islet amyloid polypeptide (IAPP) gene within the endocrine pancreas and its correlation with insular neuroendocrine peptide localization were investigated in the rat. In situ hybridization with a 35S-labelled IAPP-mRNA specific oligonucleotide probe was combined with immunocytochemistry. In situ hybridization alone showed strong autoradiographic labelling of the pancreatic islets. In situ hybridization combined with immunocytochemistry for IAPP, revealed labelling of the IAPP-immunoreactive cells. However, when in situ hybridization was combined with immunocytochemistry for proinsulin, we noted a lack of proinsulin immunoreactivity in some peripherally located autoradiographically labelled islet cells. Furthermore, combination of in situ hybridization and immunocytochemistry for somatostatin showed autoradiographic labelling of somatostatin cells to a varying degree. This was further confirmed by showing cellular co-localization of IAPP and somatostatin by immunocytochemical double staining. We conclude that IAPP is mainly synthesized in insulin cells. Additionally, a subpopulation of the somatostatin cells is capable of IAPP synthesis. This may account for the relatively small reduction in the content of IAPP-mRNA in islets compared to the marked reduction of insulin mRNA after streptozotocin-induced diabetes in rats as previously reported.
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PMID:Islet amyloid polypeptide gene expression in the endocrine pancreas of the rat: a combined in situ hybridization and immunocytochemical study. 790 97

The interactions of glucagon-like peptide-I(7-37)/(7-36)amide (GLP-I) and somatostatin-14 were characterized on the cyclic adenosine monophosphate (cAMP)-dependent signal transduction pathway and on proinsulin gene expression using mouse insulinoma beta TC-1 cells. GLP-I stimulated the activity of adenylate cyclase maximally at 1 mumol/L (151%). This effect was inhibited by 1 mumol/L somatostatin (119%). Forskolin also stimulated adenylate cyclase activity (10 mumol/L forskolin, 265%), and this action was inhibited by somatostatin (220%). Somatostatin alone left the basal adenylate cyclase activity unaltered. Somatostatin reduced the GLP-I-stimulated increase of intracellular cAMP levels (100 nmol/L GLP-I, 141%; 100 nmol/L GLP-I + 1 mumol/L somatostatin, 110%). GLP-I stimulated concentration-dependently the activity of protein kinase A (PKA), with a maximum at 10 nmol/L (181%). This action was inhibited by 100 nmol/L somatostatin (118%), but somatostatin did not influence the basal PKA activity. Furthermore, somatostatin reduced the GLP-I-induced stimulation of proinsulin gene expression (10 nmol/L GLP-I, 176%; 10 nmol/L GLP-I + 1 mumol/L somatostatin, 77%). Somatostatin itself inhibited concentration-dependently proinsulin gene expression (1 mumol/L somatostatin, 53%). These data demonstrate that GLP-I increases the activities of both adenylate cyclase and cAMP-dependent PKA, whereas somatostatin counteracts the stimulatory effect of GLP-I on adenylate cyclase activity, cAMP generation, PKA activity, and proinsulin gene expression. The interaction of both hormones occurs at the level of adenylate cyclase. Therefore, the interaction of both peptide hormones regulates downstream events, including gene expression.
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PMID:Interaction of glucagon-like peptide-I (7-37) and somatostatin-14 on signal transduction and proinsulin gene expression in beta TC-1 cells. 791 Dec 22

The immunocytochemical distribution and messenger RNA expression of the prohormone convertases PC1 and PC2 involved in the posttranslational processing of precursor proteins were analyzed in mouse and rat pancreatic islets. Immunocytochemical colocalization studies demonstrated a close association of insulin with both PC1 and PC2 in the adult mouse and rat pancreas. The coexpression of insulin with the prohormone convertases was further examined in rat pancreatic tumors induced by streptozotocin-nicotinamide treatment. These insulin-synthesizing tumors expressed PC1 and PC2, whereas insulin-silent adenomas did not. Colocalization studies demonstrated that only PC2, not PC1, colocalizes with glucagon, pancreatic polypeptide, and somatostatin. The highest levels of PC2-like immunoreactivity were observed in the glucagon-containing alpha-cells. Ontogeny studies carried out by in situ hybridization in mice showed the first detectable expression of the prohormone convertases in the pancreatic primordium at midgestation, starting for PC1 on embryonic day 11 and for PC2 on embryonic day 10. Enzyme expression was further confirmed by immunocytochemistry, which detected the presence of immunoreactive PC1- and PC2-like proteins on embryonic days 14 and 17, respectively. Taken together, our data suggest that both PC1 and PC2 play a role in proinsulin processing in vivo, whereas PC2 is a likely candidate convertase participating in the processing of proglucagon, propancreatic polypeptide, and prosomatostatin in pancreatic islets.
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PMID:Developmental expression of the prohormone convertases PC1 and PC2 in mouse pancreatic islets. 792 29

Insulin, proinsulin and C-peptide responses to intravenous glucose (glucose infusion test, GIT) and insulin sensitivity were measured in women who previously and for unexplained reasons gave birth to small-for-gestational-age infants (SGA, n = 10) or appropriate-for-gestational-age infants (AGA, n = 11). Insulin sensitivity was evaluated by two different methods, somatostatin-, insulin- and glucose infusion test (SIGIT) and Bergman's minimal model method applied to the frequently samples intravenous glucose tolerance test. The two groups were comparable with regard to age, parity and body mass index. The SGA group exhibited significantly (p < 0.01) lower early (0-10 min) and late (10-60 min) insulin, C-peptide and proinsulin responses during GIT than were seen in the control AGA group. Insulin sensitivity evaluated by the two techniques was increased in the SGA group, significantly so only with the minimal model method. The insulin sensitivity index (Si) according to Bergman was 10.98 +/- 2.10 in the SGA as compared to 4.36 +/- 1.18 x 10(-4)min-1 x uU-1 in the AGA group (antilogged values +/- 95% confidence intervals). Early insulin response (GIT) and Si values were inversely correlated (r = -0.48, p < 0.05).
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PMID:Decreased beta-cell function in women with previous small for gestational age infants. 809 83


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