glucagon receptor

• グルカゴン受容体、グルカゴンレセプター

WordNet

1. a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
2. a hormone secreted by the pancreas; stimulates increases in blood sugar levels in the blood (thus opposing the action of insulin)

PrepTutorEJDIC

1. =sense organ / 受信装置

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/06/11 11:59:01」(JST)

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Glucagon receptor
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3CZF, 4ERS
Identifiers
Symbols	GCGR; GGR
External IDs	OMIM: 138033 MGI: 99572 HomoloGene: 131 IUPHAR: glucagon receptor ChEMBL: 1985 GeneCards: GCGR Gene
Gene Ontology Molecular function • glucagon receptor activity • guanyl-nucleotide exchange factor activity • peptide hormone binding Cellular component • endosome • plasma membrane • integral to membrane Biological process • generation of precursor metabolites and energy • energy reserve metabolic process • exocytosis • adenylate cyclase-modulating G-protein coupled receptor signaling pathway • adenylate cyclase-activating G-protein coupled receptor signaling pathway • response to nutrient • regulation of blood pressure • hormone-mediated signaling pathway • small molecule metabolic process • cellular response to glucagon stimulus Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2642	14527
Ensembl	ENSG00000215644	ENSMUSG00000025127
UniProt	P47871	Q61606
RefSeq (mRNA)	NM_000160	NM_008101
RefSeq (protein)	NP_000151	NP_032127
Location (UCSC)	Chr 17: 79.76 – 79.77 Mb	Chr 11: 120.53 – 120.54 Mb
PubMed search	[1]	[2]

The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, G_s and to a lesser extent G alpha q. Stimulation of the receptor results in activation of adenylate cyclase and increased levels of intracellular cAMP. In humans, the glucagon receptor is encoded by the GCGR gene.

Glucagon receptors are mainly expressed in liver and in kidney with lesser amounts found in heart, adipose tissue, spleen, thymus, adrenal glands, pancreas, cerebral cortex, and gastrointestinal tract.

Clinical significance

A missense mutation in the GCGR gene is associated with diabetes mellitus type 2.

Inactivating mutation of glucagon receptor in humans causes resistance to glucagon and is associated with pancreatic alpha cell hyperplasia, nesidioblastosis, hyperglucagonemia, and pancreatic neuroendocrine tumors.

References

Further reading

• Levey GS, Weiss SR, Ruiz E (1975). "Characterization of the glucagon receptor in a pheochromocytoma.". J. Clin. Endocrinol. Metab. 40 (4): 720–3. doi:10.1210/jcem-40-4-720. PMID 165216. 
• Nakamura S, Rodbell M (1991). "Glucagon induces disaggregation of polymer-like structures of the alpha subunit of the stimulatory G protein in liver membranes.". Proc. Natl. Acad. Sci. U.S.A. 88 (16): 7150–4. doi:10.1073/pnas.88.16.7150. PMC 52251. PMID 1908089. 
• Horuk R, Wright DE (1983). "Partial purification and characterization of the glucagon receptor.". FEBS Lett. 155 (2): 213–7. doi:10.1016/0014-5793(82)80605-4. PMID 6303843. 
• MacNeil DJ, Occi JL, Hey PJ, et al. (1994). "Cloning and expression of a human glucagon receptor.". Biochem. Biophys. Res. Commun. 198 (1): 328–34. doi:10.1006/bbrc.1994.1046. PMID 7507321. 
• Fujisawa T, Ikegami H, Yamato E, et al. (1995). "A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the association with diabetes mellitus.". Diabetologia 38 (8): 983–5. doi:10.1007/BF00400589. PMID 7589886. 
• Unson CG, Macdonald D, Merrifield RB (1993). "The role of histidine-1 in glucagon action.". Arch. Biochem. Biophys. 300 (2): 747–50. doi:10.1006/abbi.1993.1103. PMID 8382034. 
• Chambers SM, Morris BJ (1996). "Glucagon receptor gene mutation in essential hypertension.". Nat. Genet. 12 (2): 122. doi:10.1038/ng0296-122. PMID 8563746. 
• Yamato E, Ikegami H, Takekawa K, et al. (1997). "Tissue-specific and glucose-dependent expression of receptor genes for glucagon and glucagon-like peptide-1 (GLP-1).". Horm. Metab. Res. 29 (2): 56–9. doi:10.1055/s-2007-978985. PMID 9105899. 
• Strazzullo P, Iacone R, Siani A, et al. (2001). "Altered renal sodium handling and hypertension in men carrying the glucagon receptor gene (Gly40Ser) variant.". J. Mol. Med. 79 (10): 574–80. doi:10.1007/s001090100257. PMID 11692154. 
• Shiota D, Kasamatsu T, Dib SA, et al. (2002). "Role of the Gly40Ser mutation in the glucagon receptor gene in Brazilian patients with type 2 diabetes mellitus.". Pancreas 24 (4): 386–90. doi:10.1097/00006676-200205000-00010. PMID 11961492. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
• Runge S, Gram C, Brauner-Osborne H, et al. (2003). "Three distinct epitopes on the extracellular face of the glucagon receptor determine specificity for the glucagon amino terminus.". J. Biol. Chem. 278 (30): 28005–10. doi:10.1074/jbc.M301085200. PMID 12724331. 
• Hassel S, Eichner A, Yakymovych M, et al. (2004). "Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel electrophoresis and mass spectrometry.". Proteomics 4 (5): 1346–58. doi:10.1002/pmic.200300770. PMID 15188402. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. 
• Mortensen OH, Dichmann DS, Abrahamsen N, et al. (2007). "Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha.". Gene 393 (1-2): 127–36. doi:10.1016/j.gene.2007.01.023. PMID 17374560. 

UpToDate Contents

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• 1. 2型糖尿病のGlucagon-like peptide-1をベースとした治療 glucagon like peptide 1 based therapies for the treatment of type 2 diabetes mellitus
• 2. 乳児および小児における低血糖に対するアプローチ approach to hypoglycemia in infants and children
• 3. 肥満の薬物療法 drug therapy of obesity
• 4. ペプチドホルモンのシグナル伝達および調節 peptide hormone signal transduction and regulation
• 5. 膵神経内分泌腫瘍（島細胞腫瘍）の分類、疫学、臨床症状、および局在 classification epidemiology clinical presentation and localization of pancreatic neuroendocrine tumors islet cell tumors

English Journal

• Effects of short chain fatty acid producing bacteria on epigenetic regulation of FFAR3 in type 2 diabetes and obesity.

• Remely M1, Aumueller E1, Merold C1, Dworzak S1, Hippe B1, Zanner J1, Pointner A1, Brath H2, Haslberger AG3.Author information 1Department of Nutritional Sciences, University Vienna, Vienna, Austria.2Diabetes Outpatient Clinic, Health Center South, Vienna, Austria.3Department of Nutritional Sciences, University Vienna, Vienna, Austria. Electronic address: alexander.haslberger@univie.ac.at.AbstractThe human gut microbiota and microbial influences on lipid and glucose metabolism, satiety, and chronic low-grade inflammation are known to be involved in metabolic syndrome. Fermentation end products, especially short chain fatty acids, are believed to engage the epigenetic regulation of inflammatory reactions via FFARs (free fatty acid receptor) and other short chain fatty acid receptors. We studied a potential interaction of the microbiota with epigenetic regulation in obese and type 2 diabetes patients compared to a lean control group over a four month intervention period. Intervention comprised a GLP-1 agonist (glucagon-like peptide 1) for type 2 diabetics and nutritional counseling for both intervention groups. Microbiota was analyzed for abundance, butyryl-CoA:acetate CoA-transferase gene and for diversity by polymerase chain reaction and 454 high-throughput sequencing. Epigenetic methylation of the promoter region of FFAR3 and LINE1 (long interspersed nuclear element 1) was analyzed using bisulfite conversion and pyrosequencing. The diversity of the microbiota as well as the abundance of Faecalibacterium prausnitzii were significantly lower in obese and type 2 diabetic patients compared to lean individuals. Results from Clostridium cluster IV and Clostridium cluster XIVa showed a decreasing trend in type 2 diabetics in comparison to the butyryl-CoA:acetate CoA-transferase gene and according to melt curve analysis. During intervention no significant changes were observed in either intervention group. The analysis of five CpGs in the promoter region of FFAR3 showed a significant lower methylation in obese and type 2 diabetics with an increase in obese patients over the intervention period. These results disclosed a significant correlation between a higher body mass index and lower methylation of FFAR3. LINE-1, a marker of global methylation, indicated no significant differences between the three groups or the time points, although methylation of type 2 diabetics tended to increase over time. Our results provide evidence that a different composition of gut microbiota in obesity and type 2 diabetes affect the epigenetic regulation of genes. Interactions between the microbiota and epigenetic regulation may involve not only short chain fatty acids binding to FFARs. Therefore dietary interventions influencing microbial composition may be considered as an option in the engagement against metabolic syndrome.
• Gene.Gene.2014 Mar 1;537(1):85-92. doi: 10.1016/j.gene.2013.11.081. Epub 2013 Dec 8.
• The human gut microbiota and microbial influences on lipid and glucose metabolism, satiety, and chronic low-grade inflammation are known to be involved in metabolic syndrome. Fermentation end products, especially short chain fatty acids, are believed to engage the epigenetic regulation of inflammato
• PMID 24325907

• Real-time trafficking and signaling of the glucagon-like peptide-1 receptor.

• Roed SN1, Wismann P2, Underwood CR2, Kulahin N2, Iversen H2, Cappelen KA2, Schäffer L3, Lehtonen J4, Hecksher-Soerensen J4, Secher A4, Mathiesen JM5, Bräuner-Osborne H5, Whistler JL6, Knudsen SM2, Waldhoer M2.Author information 1Department of Incretin & Islet Biology, Novo Nordisk A/S, Maaloev, Denmark; Ernest Gallo Clinic and Research Center, Department of Neurology, University of California San Francisco, San Francisco, USA. Electronic address: snro@novonordisk.com.2Department of Incretin & Islet Biology, Novo Nordisk A/S, Maaloev, Denmark.3Department of Diabetes Protein Engineering, Novo Nordisk A/S, Maaloev, Denmark.4Department of Histology and Imaging, Novo Nordisk A/S, Maaloev, Denmark.5Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.6Ernest Gallo Clinic and Research Center, Department of Neurology, University of California San Francisco, San Francisco, USA.AbstractThe glucagon-like peptide-1 incretin receptor (GLP-1R) of family B G protein-coupled receptors (GPCRs) is a major drug target in type-2-diabetes due to its regulatory effect on post-prandial blood-glucose levels. The mechanism(s) controlling GLP-1R mediated signaling are far from fully understood. A fundamental mechanism controlling the signaling capacity of GPCRs is the post-endocytic trafficking of receptors between recycling and degradative fates. Here, we combined microscopy with novel real-time assays to monitor both receptor trafficking and signaling in living cells. We find that the human GLP-1R internalizes rapidly and with similar kinetics in response to equipotent concentrations of GLP-1 and the stable GLP-1 analogues exendin-4 and liraglutide. Receptor internalization was confirmed in mouse pancreatic islets. GLP-1R is shown to be a recycling receptor with faster recycling rates mediated by GLP-1 as compared to exendin-4 and liraglutide. Furthermore, a prolonged cycling of ligand-activated GLP-1Rs was observed and is suggested to be correlated with a prolonged cAMP signal.
• Molecular and cellular endocrinology.Mol Cell Endocrinol.2014 Feb 15;382(2):938-49. doi: 10.1016/j.mce.2013.11.010. Epub 2013 Nov 22.
• The glucagon-like peptide-1 incretin receptor (GLP-1R) of family B G protein-coupled receptors (GPCRs) is a major drug target in type-2-diabetes due to its regulatory effect on post-prandial blood-glucose levels. The mechanism(s) controlling GLP-1R mediated signaling are far from fully understood. A
• PMID 24275181

• Concurrent pharmacological modification of cannabinoid-1 and glucagon-like peptide-1 receptor activity affects feeding behavior and body weight in rats fed a free-choice, high-carbohydrate diet.

• Radziszewska E, Wolak M, Bojanowska E.Author information Department of Behavioral Pathophysiology, Medical University of Lodz, Lodz, Poland.AbstractTo extend preliminary studies on the effects on food intake of the combined use of cannabinoid (CB) 1 and glucagon-like peptide-1 (GLP-1) receptor agonists and antagonists, the effect of these drugs on the feeding behavior in rats maintained on a free-choice, high-carbohydrate diet was investigated over a longer period of time. Rats were fed a standard diet for 3 days and then fed with both the standard and the high-sucrose chow. After 4 days of the high-calorie diet, the following combination treatments were administered daily by an intraperitoneal injection for the next 3 days: 1 mg/kg AM 251 (a CB1 receptor antagonist) or 1 mg/kg WIN 55,212-2 (a CB1 receptor agonist) together with 3 µg/kg exendin-4 (Ex-4, a GLP-1 receptor agonist) or 160 µg/kg exendin (9-39) [Ex (9-39), a GLP-1 receptor antagonist]. The total daily caloric intake and body weight were significantly reduced in rats treated with Ex-4 and AM 251 or WIN 55,212-2 compared with either of the drugs injected alone and the saline-injected controls. Both drug combinations selectively inhibited ingestion of the high-sucrose chow. Although Ex (9-39) administration did not significantly affect food consumption, it resulted in a marked body weight gain, indicating that the GLP-1 receptor antagonist caused a positive energy balance. It is concluded that AM 251 or WIN 55,212-2 and Ex-4, injected together, exert additive, inhibitory effects on the consumption of high-sugar food.
• Behavioural pharmacology.Behav Pharmacol.2014 Feb;25(1):53-60. doi: 10.1097/FBP.0000000000000018.
• To extend preliminary studies on the effects on food intake of the combined use of cannabinoid (CB) 1 and glucagon-like peptide-1 (GLP-1) receptor agonists and antagonists, the effect of these drugs on the feeding behavior in rats maintained on a free-choice, high-carbohydrate diet was investigated
• PMID 24370558

Japanese Journal

• 注射用抗糖尿病薬使用時の留意点 (特集 高齢者の糖尿病 : 病態・管理法の最新知見) -- (高齢者糖尿病の管理・治療上の留意点)

• 安藤 恭代,弘世 貴久
• 日本臨床 71(11), 1993-1998, 2013-11
• NAID 40019831918

• ABSTRACT 中枢神経系のグルカゴン様ペプチド1受容体シグナル伝達による褐色脂肪組織の熱産生の直接的な制御

• Lockie Sarah H.,Heppner Kristy M.,Chaudhary Nilika [他]
• Diabetes : a journal of the American Diabetes Association 6(3), 33-35, 2013-06
• NAID 40019773528

• 血管内皮細胞におけるGLP-1作動薬の抗動脈硬化作用

• 奥村 貴子,田辺 節,Nuliguli Aili,今野 一誠,伊藤 禄郎,酒井 裕幸,金澤 昭,小田原 雅人
• 東京医科大学雑誌 71(2), 135-142, 2013-04-30
• NAID 120005341596

Related Links

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Diabetes has long been viewed as a bihormonal disorder, with glucagon excess, in the setting of insulin deficiency or insulin resistance, contributing significantly to the development of hyperglycemia. Accordingly strategies for ...

• Glucagon Receptor

Although glucagon-mediated signaling effects and biological actions have been studied for years in different cell types and tissues, a major advance in our understanding of glucagon action was the cloning of the glucagon ...

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glucagon receptor

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グルカゴン受容体