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

The 24 endocrine pancreatic tumors and 14 carcinoids were examined immunohistochemically for cholecystokinin, insulin, gastrin, GIP, glucagon, sercretin, VIP, motilin, neurotensin, pancreatic polypeptide (PP), somatostatin, and ACTH. In 12 tumors of the pancreas more than one peptide-containing cell type was observed. The clinical symptoms showed hypersecretion of only one of the hormones, however. The midgut carcinoids (jejunum, appendix) represented the classical view of the carcinoid as an argentaffin cell tumor secreting 5-hydroxytryptamine. Tumors originating in the foregut (bronchus, stomach, duodenum) and hindgut carcinoids (rectum) were nonargentaffine, containing and secreting various polypeptide hormones. We conclude that light microscopic immunohistochemical methods are useful in distinguishing endocrine from nonendocrine tumors and multihormonal syndromes (MEA) in the classification of predominant hormone-secreting tumors.
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PMID:[Endocrine tumors of the gastrointestinal and pancreatic systems. Multiple endocrine adenoma from another viewpoint]. 610 39

Prospective screening was carried out in 12 members of three families with multiple endocrine adenopathies, type I (MEA,I) and in 14 patients with no multiple endocrine adenopathies with and without other endorcinopathies. Elevated basal and responsive (after a meal) plasma concentrations of a relatively new candidate-hormone, human pancreatic polypeptide (hPP), were associated with pancreatic apudoma tumors in three asymptomatic patients with multiple endocrine adenopathies, type I. Two of these patients had excision of the tumors that resulted in normal plasma hPP concentrations postoperatively. Both tumors contained hPP predominantly by immunocytochemistry; one, a pure pancreatic polypeptide apudoma, was studied extensively demonstrating also by radioimmunoassay a high content of hPP and negligible amounts of insulin, glucagon, somatostatin, vasoactive intestinal polypeptide and gastrin. In this patient plasma concentrations of other polypeptides including insulin, glucagon, somatostatin, vasoactive intestinal polypeptide, gastrin, parathyrin, thyrocalcitonin, prolactin, corticotropin, growth hormone, thyrtropin and amine, serotonin, were within normal limits. The other patient, after excision of an hPP-detected pancreatic mixed hPP-gastrinoma, also became eugastrinemic postoperatively. Normal basal plasma hPP concentrations, but with exaggerated hPP responses to a meal in 11 patients, were associated with various combinations of islet cell hyperplasia, antral G cell hyperplasia with moderate hypergastrinemia and parathyroid hyperplasia. The patients with multiple endocrine adenopathies who have demonstrated this type of increased hPP response to a meal have not been operated on but are at risk for islet hyperplasia. Four of the 12 patients with multiple endocrine adenopathies, type I, with both normal basal and normally responsive hPP concentrations have no evidence as yet of pancreatic involvement.
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PMID:Pancreatic polypeptide as screening marker for pancreatic polypeptide apudomas in multiple endocrinopathies. 624 7

Interactions between two classes of receptors have been observed in several cell lines and preparations. The aim of this work was to assess the impact of simultaneous stimulation of endothelial muscarinic and alpha2-adrenergic receptors (alpha2-AR) on vascular reactivity. Rabbit middle cerebral arteries were isolated and changes in isometric tension were recorded in the presence of indomethacin. Inhibition of nitric oxide (NO) synthase with Nomega-nitro-L-arginine (L-NOARG, 100 micromol l(-1)) revealed alpha-AR-dependent contractions. Pre-addition of acetylcholine (ACH, 1 micromol l(-1)) augmented oxymetazoline (OXY, 10 micromol l(-1), alpha2-AR agonist)-, but decreased phenylephrine (PE, 10 micromol(-1), alpha1-AR agonist)-induced contraction (P<0.05). The effects of ACH were endothelium-dependent. Vessels were precontracted with 40 mmol l(-1) KCl-physiological salt solution (PSS) in the absence of L-NOARG, or PE or OXY in the presence of L-NOARG. In the presence of high external K+ or PE, ACH induced a potent relaxation (P<0.05). In the presence of OXY, however, ACH mediated contraction (P<0.05). After pertussis toxin (PTX, inactivator of Galpha(i/o) proteins) pre-treatment, alpha2-AR-dependent contractions were abolished. Forty mmol l(-1) KCl-PSS induced contraction was not altered by PTX whereas ACH-induced relaxation was augmented (P<0.05). To investigate if endothelin-1 (ET-1) intervened in the endothelium-dependent contractile response to ACH in the presence of OXY-dependent tone, vessels were incubated in the presence of BQ123 (1 micromol l(-1)), an ETA receptor antagonist. OXY-mediated tone was not affected by BQ123; however, ACH-induced contraction was reversed to a relaxation (P<0.05). These data indicate that activation of endothelial alpha2-AR triggers an endothelium-dependent, ET-1 mediated, contraction to ACH. This suggests that activation of alpha2-AR affects muscarinic receptor/G protein coupling leading to an opposite biological effect.
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PMID:Functional cross-talk between endothelial muscarinic and alpha2-adrenergic receptors in rabbit cerebral arteries. 986 46

Obesity and insulin resistance are primary risk factors for Non-Alcoholic Fatty Liver Disease (NAFLD). NAFLD is generally exhibited by non-progressive simple steatosis. However, a significant subset of patient's progress to nonalcoholic steatohepatitis (NASH) that is defined by the presence of steatosis, inflammation and hepatocyte injury with fibrosis. Unfortunately, there are no approved therapies for NAFLD or NASH and therefore therapeutic approaches are urgently needed. Niclosamide is an U.S. Food and Drug Administration (FDA)-approved anthelmintic drug that mediates its effect by uncoupling oxidative phosphorylation. Niclosamide and its salt forms, Niclosamide Ethanolamine (NEN), and Niclosamide Piperazine (NPP) have shown efficacy in murine models of diet induced obesity characterized by attenuation of the prominent fatty liver disease phenotype and improved glucose metabolism. While the exact mechanism(s) underlying these changes remains unclear, the ability to uncouple oxidative phosphorylation leading to increased energy expenditure and lipid metabolism or attenuation of PKA mediated glucagon signaling in the liver have been proposed. Unfortunately, niclosamide has very poor water solubility, leading to low oral bioavailability. This, in addition to mitochondrial uncoupling activity and potential genotoxicity have reduced enthusiasm for its clinical use. More recently, salt forms of niclosamide, NEN and NPP, have demonstrated improved oral bioavailability while retaining activity. This suggests that development of safer more effective niclosamide derivatives for the treatment of NAFLD and Type 2 Diabetes may be possible. Herein we explored the ability of a series of N-substituted phenylbenzamide derivatives of the niclosamide salicylanilide chemotype to attenuate hepatic steatosis using a novel phenotypic in vitro model of fatty liver and the high fat diet-fed mouse model of diet induced obesity. These studies identified novel compounds with improved pre-clinical properties that attenuate hepatic steatosis in vitro and in vivo. These compounds with improved drug properties may be useful in alleviating symptoms and protection against disease progression in patients with metabolic syndrome and NAFLD.
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PMID:N-substituted phenylbenzamides of the niclosamide chemotype attenuate obesity related changes in high fat diet fed mice. 3035 71