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)

This review focuses on precursor lesions of gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs). There are three conditions that are associated with hyperplastic changes in endocrine cells preceding GEP-NETs: autoimmune chronic atrophic gastritis or multiple endocrine neoplasia type 1 (MEN1) with gastric enterochromaffin-like (ECL) cell hyperplasia; MEN1 with gastrin and somatostatin cell hyperplasia in the duodenum and glucagon cell hyperplasia in the islets of the pancreas; and inflammatory bowel disease with endocrine cell hyperplasia in the colon. In gastric ECL cell hyperplasia, it is assumed that hypergastrinemia promotes the growth of the ECL cells of the corpus mucosa and leads to hyperplasia and neoplasia. In the duodenum and the pancreas, the MEN1-associated germline mutation of the menin gene obviously causes hyperplasia of the gastrin and somatostatin cells (duodenum) and the glucagon cells (pancreas), resulting in multifocal development of tumors. These tumors show allelic deletion of the MEN1 gene, whereas the precursor lesions retain their heterozygosity. The endocrine cell hyperplasia in the colon described in inflammatory bowel disease has neither a genetic nor a definite hormonal background.
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PMID:Endocrine precursor lesions of gastroenteropancreatic neuroendocrine tumors. 1805 64

Inflammatory bowel disease (IBD) is a chronic, debilitating disease associated with severe damage to the intestinal mucosa. Glucagon-like peptide-2 (GLP-2) is a potent and specific gastrointestinal growth factor that is demonstrating therapeutic potential for the prevention or treatment of an expanding number of intestinal diseases, including short bowel syndrome (SBS), small bowel enteritis and IBD. The biological activity of GLP-2 is limited due to proteolytic inactivation by the protease dipeptidyl peptidase (DP)IV. Inhibitors of DPIV activity may represent a novel strategy to prolong the growth promoting actions of GLP-2. This review outlines evidence for the clinical application of GLP-2, its degradation resistant analogue, Teduglutide, and novel DPIV inhibitors in efficacy studies utilizing pre-clinical models of intestinal damage, in particular IBD.
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PMID:Growth factor based therapies and intestinal disease: is glucagon-like peptide-2 the new way forward? 1932 85

The pharmacological application of intestinal growth factors has been recognized because of the protective and reparative actions of these factors in the intestinal tract. This review highlights the use of keratinocyte growth factor (KGF), IGF-1 and glucagon-like peptide 2 (GLP-2) in efficacy studies of intestinal damage; the results from these studies support potential clinical applications of these factors in treating intestinal diseases. In particular, GLP-2 has been assessed in preclinical and clinical investigations for its capacity to prevent or treat an increasing number of intestinal diseases, including short bowel syndrome, chemotherapy-induced intestinal mucositis and inflammatory bowel disease.
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PMID:The use of GLP-2 and related growth factors in intestinal diseases. 2033 92

Glucose-6-phosphatase deficiency (G6P deficiency), or glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea). Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty), generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma) and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency). GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia) which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib). Mutations in the genes G6PC (17q21) and SLC37A4 (11q23) respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most commonly confirmed by G6PC (GSDIa) or SLC37A4 (GSDIb) gene analysis, and the indications of liver biopsy to measure G6P activity are getting rarer and rarer. Differential diagnoses include the other GSDs, in particular type III (see this term). However, in GSDIII, glycemia and lactacidemia are high after a meal and low after a fast period (often with a later occurrence than that of type I). Primary liver tumors and Pepper syndrome (hepatic metastases of neuroblastoma) may be evoked but are easily ruled out through clinical and ultrasound data. Antenatal diagnosis is possible through molecular analysis of amniocytes or chorionic villous cells. Pre-implantatory genetic diagnosis may also be discussed. Genetic counseling should be offered to patients and their families. The dietary treatment aims at avoiding hypoglycemia (frequent meals, nocturnal enteral feeding through a nasogastric tube, and later oral addition of uncooked starch) and acidosis (restricted fructose and galactose intake). Liver transplantation, performed on the basis of poor metabolic control and/or hepatocarcinoma, corrects hypoglycemia, but renal involvement may continue to progress and neutropenia is not always corrected in type Ib. Kidney transplantation can be performed in case of severe renal insufficiency. Combined liver-kidney grafts have been performed in a few cases. Prognosis is usually good: late hepatic and renal complications may occur, however, with adapted management, patients have almost normal life span. DISEASE NAME AND SYNONYMS: Glucose-6-phosphatase deficiency or G6P deficiency or glycogen storage disease type I or GSDI or type I glycogenosis or Von Gierke disease or Hepatorenal glycogenosis.
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PMID:Glucose-6-phosphatase deficiency. 2159 42

The peroral pneumocolon represents a time-honored but somewhat forgotten and underutilized technique for improved ileocecal evaluation at small bowel fluoroscopy. The peroral pneumocolon entails fluoroscopically guided gaseous insufflation per rectum following the arrival of barium at the cecum at conventional small bowel follow-through examination. In most cases, high-quality double contrast evaluation of the terminal ileum can be achieved, often superior to enteroclysis examination for this critical location. The peroral pneumocolon improves diagnostic confidence, including assessment of disease activity, and may result in a reversal of the diagnostic impression. This simple procedure will be discussed and a spectrum of fluoroscopic findings with CT and endoscopic correlation will be provided to demonstrate the added yield of this technique in the evaluation of known or suspected Crohn's disease. Application of the pneumocolon technique to CT for combined small and large bowel evaluation ("CT coloenterography") will also be discussed, which represents an attractive new option for investigating inflammatory bowel disease and other bowel-related conditions. Through the use of automated low-pressure carbon dioxide delivery per rectum, supplemented by IV glucagon for relaxation of the ileocecal valve, a CT-based pneumocolon examination may prove to be a useful hybrid technique for bowel evaluation in the future.
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PMID:The peroral pneumocolon revisited: a valuable fluoroscopic and CT technique for ileocecal evaluation. 2168 93

OBJECTIVE. Inflammatory bowel disease (IBD) is a chronic debilitating disease associated with severe damage to the intestinal mucosa. Glucagon-like peptide-2 (GLP-2) is a potent and specific gastrointestinal growth factor. GLP-2 released from enteroendocrine cells is inactivated by dipeptidyl peptidase-4 (DPP-4). The aim of this study was to examine whether the DPP-4 inhibitor anagliptin improves experimental murine colitis. MATERIAL AND METHODS. Male C57BL/6 mice aged 8 weeks were exposed to 1.5% dextran sulfate sodium (DSS) in drinking water for 7 days to induce experimental colitis. Anagliptin (0.1% in diet) was administrated from 2 days before the beginning of DSS to 7 days after the end of DSS. Changes in body weight and disease activity index were evaluated daily. Histological colitis severity, cellular proliferation and gene expression were determined in colonic tissues. RESULTS. Treatment with anagliptin clearly improved body weight loss and disease activity index in the recovery phase. Histological score in the DSS + anagliptin group at day 14 was significantly lower than that in the DSS alone group. Treatment with anagliptin increased the Ki67-positive rate at days 10 and 14, and tended to increase insulin-like growth factor-1 mRNA expression in the DSS + anagliptin group. CONCLUSION. In this model of experimental colitis, the DPP-4 inhibitor anagliptin facilitated the restoration of mucosal damage, thereby resulting in the acceleration of healing. These findings suggest a new and novel therapeutic approach for the treatment of IBD.
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PMID:Dipeptidyl peptidase-4 inhibitor anagliptin facilitates restoration of dextran sulfate sodium-induced colitis. 2404 94

Cross-sectional imaging forms an important alternative and complimentary tool to endoscopy in aiding the clinician with diagnosis and management of pediatric inflammatory bowel disease (IBD). The purpose of the study was to evaluate the feasibility of an optimized Magnetic Resonance Enterography (MRE) protocol in the evaluation of patients with suspected IBD. 31 children (18 boys and 13 girls) were evaluated by a pediatric gastroenterologist prior to MRE and given a grading for clinical severity of disease. Imaging was then performed with oral contrast and a tailored protocol using fast T1/T2 weighted pulse sequences. Additionally, contrast and glucagon were administered intravenously. Imaging findings were then correlated with the clinical data. Excellent distension was achieved in the small bowel. The majority of the studies were of diagnostic quality with no motion artifacts. Imaging findings showed statistically significant correlation with disease activity. An optimized pediatric MRE protocol is feasible and correlates well with clinical disease activity. This in turn aids the clinician in the management of children with this chronic debilitating disease.
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PMID:Feasibility of an optimized MR enterography protocol in the evaluation of pediatric inflammatory bowel disease. 2422 93

The glucagon-like peptide 2 (GLP-2) is an intestinotrophic hormone with growth promoting and anti-inflammatory actions. However, the full biological functions of GLP-2 and the localization of its receptor (GLP-2R) remain controversial. Among cell lines tested, the expression of GLP-2R transcript was detected in human colonic myofibroblasts (CCD-18Co) and in primary culture of rat enteric nervous system but not in intestinal epithelial cell lines, lymphocytes, monocytes, or endothelial cells. Surprisingly, GLP-2R was expressed in murine (GLUTag), but not human (NCI-H716) enteroendocrine cells. The screening of GLP-2R mRNA in mice organs revealed an increasing gradient of GLP-2R toward the distal gut. An unexpected expression was detected in the mesenteric fat, mesenteric lymph nodes, bladder, spleen, and liver, particularly in hepatocytes. In two mice models of trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis, the colonic expression of GLP-2R mRNA was decreased by 60% compared with control mice. Also, GLP-2R mRNA was significantly downregulated in intestinal tissues of inflammatory bowel disease patients. Therapeutically, GLP-2 showed a weak restorative effect on intestinal inflammation during TNBS-induced colitis as assessed by macroscopic score and inflammatory markers. Finally, GLP-2 treatment accelerated mouse liver regeneration following partial hepatectomy as assessed by histological and molecular analyses. In conclusion, the limited therapeutic effect of GLP-2 on colonic inflammation dampens its utility in the management of severe inflammatory intestinal disorders. However, the role of GLP-2 in liver regeneration is a novelty that might introduce GLP-2 into the management of liver diseases and emphasizes on the importance of elucidating other extraintestinal functions of GLP-2.
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PMID:Glugacon-like peptide-2: broad receptor expression, limited therapeutic effect on intestinal inflammation and novel role in liver regeneration. 2487 97

Magnetic resonance enterography (MRE) now plays a central role in diagnosing pediatric inflammatory bowel disease (IBD), and its role in other intestinal pathologies such as scleroderma is gradually expanding. MRE helps distinguish between Crohn disease and ulcerative colitis, defining extent and severity. Standard MRE protocols can be optimized in children and adolescents to be diagnostic and well tolerated, both of which are important with increasing use of serial MRE in pediatric IBD for monitoring treatment response and evaluating complications. MRI is especially suited to this role given its lack of ionizing radiation. MRE compliance can be improved through patient education. Differing from adult MRE, pediatric MRE protocols use weight-based formulas to calculate oral and intravenous contrast media and antispasmodic agent doses, using either hyoscine-N-butylbromide or glucagon. Nausea is more commonly experienced with glucagon; however vomiting occurs in <10% of children with either agent. Standard and advanced sequences applied in adults are also used in children and adolescents. These include static and cinematic balanced steady-state free precession sequences, single-shot T2-weighted sequences, diffusion-weighted imaging and pre- and post-contrast 3-D T1-weighted gradient echo sequences. Magnetization transfer imaging and quantitative assessment of bowel to distinguish inflammation and fibrosis are not yet standard in pediatric MRE, but show promise.
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PMID:How we do it: MR enterography. 2722

Numerous endocrine cell subtypes exist within the intestinal mucosa and produce peptides contributing to the regulation of critical physiological processes including appetite, energy metabolism, gut function, and gut health. The mechanisms of action and the extent of the physiological effects of these enteric peptides are only beginning to be uncovered. One peptide in particular, glucagon-like peptide 2 (GLP-2) produced by enteroendocrine L cells, has been fairly well characterized in rodent and swine models in terms of its ability to improve nutrient absorption and healing of the gut after injury. In fact, a long-acting form of GLP-2 recently has been approved for the management and treatment of human conditions like inflammatory bowel disease and short bowel syndrome. However, novel functions of GLP-2 within the gut continue to be demonstrated, including its beneficial effects on intestinal barrier function and reducing intestinal inflammation. As knowledge continues to grow about GLP-2's effects on the gut and its mechanisms of release, the potential to use GLP-2 to improve gut function and health of food animals becomes increasingly more apparent. Thus, the purpose of this review is to summarize: (1) the current understanding of GLP-2's functions and mechanisms of action within the gut; (2) novel applications of GLP-2 (or stimulators of its release) to improve general health and production performance of food animals; and (3) recent findings, using dairy calves as a model, that suggest the therapeutic potential of GLP-2 to reduce the pathogenesis of intestinal protozoan infections.
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PMID:Glucagon-like peptide 2 and its beneficial effects on gut function and health in production animals. 2734 24


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