Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new model of a reversible long-term pancreatic fistula was used on an alert, unrestrained dog to test the effect of four substances of the GEP system on the exocrine pancreatic function. The results indicate that SST significantly inhibits not only the basal secretion but also the stimulated secretion of volume, bicarbonate, and trypsine. Calcitonine inhibits only the stimulated secretion whereas PGE1 inhibits only the secretin-stimulated output of trypsine. Glucagon inhibits secretin stimulation in all three parameters.
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PMID:[Long-term study of endocrine inhibition of exocrine pancreas secretion in the conscious dog]. 75 88

Immunohistochemistry on tissues of larval lampreys, Petromyzon marinus L., was used to determine the distribution of invariant somatostatin-14 (SST-14) and lamprey somatostatin-34 (SST-34) in the brain while antisera against porcine peptide tyrosine tyrosine (PYY), human neuropeptide Y (NPY), anglerfish peptide YG (aPY), salmon glucagon-like peptide (GLP), SST-14, and SST-34 were used in studies of the pancreas and anterior intestine. In the brain, SST-14 is the major form of somatostatin. SST-14- and SST-34-immunoreactive nerve fibers are distributed throughout the telencephalon, diencephalon, and mesencephalon. In the latter region SST-14 immunoreactivity is concentrated in nerve tracts in the nucleus interpeduncularis. Nerve cells within the olfactory bulbs are immunoreactive only to anti-SST-34. Cells immunostained with anti-SST-14 were localized within the ependymal and subependymal layers of the pars ventralis hypothalami and the subependymal layers of the pars dorsalis thalami. SST-14-immunoreactive perikarya are also distributed within the tegmentum mesencephali. Nerve fibers and cells immunoreactive to anti-SST-34 are detected in the pars ventralis hypothalami but these cells do not colocalize SST-14. Pancreatic islets, distributed within the epithelium and in the submucosal connective tissue at the esophageal-intestinal junction, are only immunoreactive to anti-insulin. The antisera revealed three distinct cell types in the intestinal epithelium: type 1 colocalizes aPY, NPY, and PYY; type 2 colocalizes SST-14 and SST-34; and type 3 demonstrates immunoreactivity only to anti-SST-34. Immunoreactivity to anti-GLP is absent.
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PMID:Distribution of two forms of somatostatin and peptides belonging to the pancreatic polypeptide family in tissues of larval lampreys, Petromyzon marinus L.: an immunohistochemical study. 167 24

Invariant somatostatin-14 (SST-14) and somatostatin-25 (SST-25), isolated from coho salmon pancreas (Plisetskaya et al., 1986a) are likely coded by two distinct somatostatin genes. The present study was undertaken to investigate whether these genes are expressed in the same or in different cell types in the pancreatic islets and in the brain of two salmonids: rainbow trout and coho salmon. Antibodies generated against SST-14, mammalian (m) SST-28(1-14), salmon (s) SST-25, salmon insulin, and salmon glucagon were used as immunocytochemical probes. Two distinct cell types containing SSTs were revealed in the pancreas of both salmonid species: one cell type immunoreactive to both SST-14 and mSST-28(1-14) and the other cell type immunoreactive only to sSST-25. The SST-14/mSST-28(1-14)-positive cells were limited to the more central parts of the islets, in apposition to the insulin-positive cells: sSST-25-positive cells were located more peripherally and were associated topographically with the glucagon-positive cells. In contrast to the pancreas, neurons in the neurohypophysis and hypothalamus of the rainbow trout and coho salmon contained only SST-14-like and mSST-28(1-14)-like immunoreactivities, while immunoreactivity to sSST-25 was completely absent. These results suggest that differentiation in the pancreas and brain of salmonid fishes results in cell types in which SST genes are separately expressed. The close topographical association of sSST-25 with glucagon cells, and of SST-14 with insulin cells, in the pancreatic islets implies yet unknown functional regulatory relationships that require detailed study.
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PMID:Different cellular distributions of two somatostatins in brain and pancreas of salmonids, and their associations with insulin- and glucagon-secreting cells. 289 14

Using a new model of a reversible pancreatic fistula which allows the long-term-investigation under nearly physiological conditions on the unrestrained dog, we tested the effect of somatostatin (50 micrograms), calcitonin (4 micrograms), glucagon (1 microgram), and prostaglandin E1 (150 micrograms) on the exocrine pancreatic function in 45 experiments over a period of 13 h: SST inhibits the basal as well as the secretin or CCK-stimulated secretion: calcitonin shows inhibition of the stimulated secretion only; glucagon blocks the secretin-stimulated pancreatic function; and PGE1 reduces the bicarbonate concentration and trypsin output in secretin stimulation, but in one of the two series it stimulates the basal secretion.
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PMID:The effect of SST, glucagon, calcitonin and PGE1 on exocrine pancreatic secretion in the unrestrained dog in long-term experiments. 611 65

The cell types within the endocrine pancreatic tissue and anterior intestine of larvae and juveniles of representatives of the two southern-hemisphere families (Mordaciidae and Geotriidae) were compared, using immunohistochemistry and antisera against insulin (lamprey, bovine), two somatostatins (SST-14, -34), two PP-family peptides (aPY, NPY), and salmon glucagon and glucagon-like peptide (GLP). Cells of the islets and some anterior intestinal cells in larval Mordacia mordax showed intense immunoreactivity (IR) to the two insulin antisera. In contrast, immunoreactivity to these antisera in the islets of larval Geotria australis was restricted to antibovine insulin and even then the staining was weak. The islet cells did not IR with other antisera, but IR to aPY and NPY antisera was noted in a few intestinal cells of both species and cells in the intestine of G. australis were positively stained with antiSST-14 and/or -34. The single islet organ of adults of both species consisted only of antiinsulin-IR, B cells, and D cells, which were IR with only antiSST-14. Although IR was not seen in islet tissue to antisera against aPY, NPY, glucagon, and GLP, four cell types were identified in the intestinal epithelium in both species based on their IR to these antisera and the two antiSSTs. A fifth cell type IR to the two insulin antisera was recognized in adult M. mordax. The types and IR of endocrine cells in the enteropancreatic system of two southern-hemisphere lamprey families are compared with those of the Petromyzontidae, the single family of holarctic lampreys. Differences are discussed in relation to variations in hormone processing and whether they are a consequence of varied ontogenic and phylogenetic history among the extant Petromyzontiformes.
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PMID:An immunohistochemical study of enteropancreatic endocrine cells in larvae and juveniles of the southern-hemisphere lampreys Geotria australis and Mordacia mordax. 790 50

The identification and distribution of endocrine cells within the gastro-entero-pancreatic (GEP) system of five species of the Osteoglossomorpha (Osteoglossum bicirrhosum, Scleropages jardini, Pantodon buchholzi, Notopterus chitala and Gnathonemus petersii) were analyzed by immunohistochemistry. Four immunoreactive cell types were identified within the pancreatic islets (A, B, D, and F cells), using antisera directed against mammalian insulin (m-INS), somatostatins (SST-14, SST-25), and members of the pancreatic polypeptide (aPY, NPY, PYY) and glucagon (GLU, GLP) families. The B cells were located throughout the center of the islets in the five species and, in general, D cells had a similar distribution. However, immunoreactivity to anti-somatostatins varied between four of the species and G. petersii, which showed less intensely stained D cells in the islets, but greater SST immunoreactivity in both the intestinal and the stomach epithelia than in comparable epithelia of other species. For peptides of both the pancreatic polypeptide and the glucagon families, the immunoreactivity was detected at the periphery of the islets, and there was a suggestion of an interfamily colocalization of peptides in some cells. In addition, glucagon family peptides showed a scattered immunoreactivity throughout the central portion of the islets. A moderately abundant number of cells in the intestine were immunoreactive to the PP family antisera in all five species. However, immunoreactivities to GLU, GLP, SST, and m-INS antisera were variable in intestinal cells of the species. Immunoreactivity with sera raised against m-INS and PYY was also observed in the stomach of P. buchholzi. The significance of these findings is discussed in both ontogenetic and phylogenetic contexts with respect to the GEP system in actinopterygian fishes and with respect to the possibility of variable processing of prohormones in the different organs of these osteoglossomorphs.
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PMID:Immunohistochemical studies of the endocrine cells within the gastro-entero-pancreatic system of Osteoglossomorpha, an ancient teleostean group. 957 Sep 33

We have developed a panel of rabbit polyclonal antipeptide antibodies against the five human somatostatin receptor subtypes (hSSTR1-5) and used them to analyze the pattern of expression of hSSTR1-5 in normal human islet cells by quantitative double-label confocal fluorescence immunocytochemistry. All five hSSTR subtypes were variably expressed in islets. The number of SSTR immunopositive cells showed a rank order of SSTR1 > SSTR5 > SSTR2 > SSTR3 > SSTR4. SSTR1 was strongly colocalized with insulin in all beta-cells. SSTR5 was also an abundant isotype, being colocalized in 87% of beta-cells. SSTR2 was found in 46% of beta-cells, whereas SSTR3 and SSTR4 were relatively poorly expressed. SSTR2 was strongly colocalized with glucagon in 89% of alpha-cells, whereas SSTR5 and SSTR1 colocalized with glucagon in 35 and 26% of alpha-cells, respectively. SSTR3 was detected in occasional alpha-cells, and SSTR4 was absent. SSTR5 was preferentially expressed in 75% of SST-positive cells and was the principal delta-cell SSTR subtype, whereas SSTR1-3 were colocalized in only a few delta-cells, and SSTR4 was absent. These studies reveal predominant expression of SSTR1, SSTR2, and SSTR5 in human islets. Beta-cells, alpha-cells, and delta-cells each express multiple SSTR isoforms, beta-cells being rich in SSTR1 and SSTR5, alpha-cells in SSTR2, and delta-cells in SSTR5. Although there is no absolute specificity of any SSTR for an islet cell type, SSTR1 is beta-cell selective, and SSTR2 is alpha-cell selective. SSTR5 is well expressed in beta-cells and delta-cells and moderately well expressed in alpha-cells, and thereby it lacks the islet cell selectivity displayed by SSTR1 and SSTR2. Subtype-selective SSTR expression in islet cells could be the basis for preferential insulin suppression by SSTR1-specific ligands and of glucagon inhibition by SSTR2-selective compounds.
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PMID:Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis. 989 25

The cellular composition and topography of the pancreatic islet of Oreochromis niloticus, now known to be a donor source for islet xenotransplantation studies, were characterized. Whole tilapia islets were harvested using an enzymatic method and then further digested into single-cell preparations. Cell cytospin preparations of islet cells and paraffin sections of whole islets were stained using antisera against tilapia insulin, human glucagon, salmon somatostatin-25 (SST-25), human somatostatin-14 (SST-14), and salmon peptide tyrosine-tyrosine (PYY) using the immunoperoxidase method. Cell counts, performed on cytospin preparations using a Quantimet 570 computerized image analysis system, revealed that O. niloticus islets contained 78% endocrine cells and 22% immunonegative cells (i. e., mainly nucleated erythrocytes and rare tissue eosinophils). The proportions of immunopositive endocrine cell types were: 42.3% insulin immunopositive cells, 11.5% glucagon immunopositive cells, 23.1% SST-25 immunopositive cells, 21.8% SST-14 immunopositive cells, and 1.3% PYY immunopositive cells. Islet cell topography was evaluated using histologic sections of whole endocrine pancreata including large, medium, and small islets. Round to polygonal insulin immunopositive cells with round central nuclei were distributed in clusters throughout both the principal and the smaller islets. Elongate SST-14 immunopositive cells were closely associated with the clusters of insulin immunopositive cells; both were surrounded by SST-25 immunopositive cells, which were similar in shape to the insulin immunopositive cells. There were elongate glucagon immunopositive cells throughout the islets, whereas the PYY immunopositive cells were restricted to the periphery and to channels of fibrovascular connective tissue penetrating the islets.
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PMID:Immunocytochemical characterization of the pancreatic islet cells of the Nile Tilapia (Oreochromis niloticus). 1009 58

Pancreatic development and the relationship of the islets with the pancreatic, hepatic, and bile ducts were studied in the Nile tilapia, Oreochromis niloticus, from hatching to the onset of maturity at 7 months. The number of islets formed during development was counted, using either serial sections or dithizone staining of isolated islets. There was a general increase in islet number with both age and size. Tilapia housed in individual tanks grew more quickly and had more islets than siblings of the same age left in crowded conditions. The pancreas is a compact organ in early development, and at 1 day posthatch (dph) a single principal islet, positive for all hormones tested (insulin, SST-14, SST-28, glucagon, and PYY), is partially surrounded by exocrine pancreas. However, the exocrine pancreas becomes more disseminated in older fish, following blood vessels along the mesenteries and entering the liver to form a hepatopancreas. The epithelium of the pancreatic duct system from the intercalated ducts to the main duct entering the duodenum was positive for glucagon and SST-14 in 8 and 16 dph tilapia. Individual insulin-immunopositive cells were found in one specimen. At this early stage in development, therefore, the pancreatic duct epithelial cells appear to be pluripotent and may give rise to the small islets found near the pancreatic ducts in 16-37 dph tilapia. Glucagon, SST-14, and some PPY-positive enteroendocrine cells were present in the intestine of the 8 dph larva and in the first part of the intestine of the 16 dph juvenile. Glucagon and SST-14-positive inclusions were found in the apical cytoplasm of the mid-gut epithelium of the 16 dph tilapia. These hormones may have been absorbed from the gut lumen, since they are produced in both the pancreatic ducts and the enteroendocrine cells. At least three hepatic ducts join the cystic duct to form the bile duct, which runs alongside the pancreatic duct to the duodenum.
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PMID:Development of the islets, exocrine pancreas, and related ducts in the Nile tilapia, Oreochromis niloticus (Pisces: Cichlidae). 1528 Oct 64

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumors, mainly localized in the gastrointestinal system. What characterizes NENs is the expression of hormone receptors on the tumor cell surface, making them accessible for diagnostic and therapeutic approaches (theranostics) using radiolabelled peptides. Somatostatin receptors subtype-two (SST2) play an important role in NENs since they are overexpressed and homogeneously distributed at the surface of the majority of NENs. Accordingly, targeting SST2 for diagnostic and therapeutic purposes has been established. Current research aims at upregulating its expression by epigenetic treatment or improving its targeting via use of alternative radioligands. In addition, recent data suggest a future role of SST antagonists as a diagnostic tool and a potential therapeutic option. Another promising target is the glucagon-like peptide-1 (GLP-1) receptor. Targeting GLP-1R using exendin-4 (GLP-1 analogue) has a high sensitivity for the localization of the often SST2-negative sporadic insulinomas and insulinomas in the context of multiple endocrine neoplasia type-1. Further options for patients with insufficient expression of SST2 involve metaiodobenzylguanidine (MIBG) and the molecular target C-X-C motif chemokine receptor-4 (CXCR4), which have been evaluated for potential theranostic approach in symptomatic NENs or dedifferentiated tumors. Recently, new targets such as the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the fibroblast activation protein (FAP) have been identified in NENs. Finally, minigastrin - a ligand targeting the cholecystokinin-2 (CCK2) receptors in medullary thyroid carcinoma and foregut neuroendocrine tumors - may improve future management of these diseases with currently limited therapeutic options. This review summarises the current approaches and future challenges of diagnostic and therapeutic evaluations in neuroendocrine neoplasms.
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PMID:Theranostics in neuroendocrine tumors: an overview of current approaches and future challenges. 3249 50


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