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Glucagon
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| PDB rendering based on 1d0r. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography | ||
| Available structures: 1d0r, 1gcn, 1kx6, 2g49 | ||
| Identifiers | ||
| Symbol(s) | GCG; GLP1; GLP2; GRPP | |
| External IDs | OMIM: 138030 MGI: 95674 HomoloGene: 1553 | |
| RNA expression pattern | ||
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| Orthologs | ||
| Human | Mouse | |
| Entrez | 2641 | 14526 |
| Ensembl | ENSG00000115263 | ENSMUSG00000000394 |
| Uniprot | P01275 | P55095 |
| Refseq | NM_002054 (mRNA) NP_002045 (protein) |
NM_008100 (mRNA) NP_032126 (protein) |
| Location | Chr 2: 162.71 - 162.71 Mb | Chr 2: 62.28 - 62.28 Mb |
| Pubmed search | [1] | [2] |
Glucagon is an important hormone involved in carbohydrate metabolism. Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body Carbohydrate metabolism denotes the various biochemical processes responsible for the formation, breakdown and interconversion of Carbohydrates Produced by the pancreas, it is released when the glucose level in the blood is low (hypoglycemia), causing the liver to convert stored glycogen into glucose and release it into the bloodstream. The pancreas is a Gland organ in the digestive and Endocrine system of Vertebrates. Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood The liver is a vital organ in the human body and is present in Vertebrates and some other animals Glycogen is a Polysaccharide of Glucose (Glc which functions as the secondary short term energy storage in Animal cells Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. The action of glucagon is thus opposite to that of insulin, which instructs the body's cells to take in glucose from the blood in times of satiation. Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance
Contents |
History
In the 1920s, Kimball and Murlin studied pancreatic extracts and found an additional substance with hyperglycemic properties. The 1920s is sometimes referred to as the " Jazz Age " or the " Roaring Twenties " when speaking about the United States and Canada The pancreas is a Gland organ in the digestive and Endocrine system of Vertebrates. Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an excessive amount of Glucose circulates in the Blood plasma They described glucagon in 1923. [1] The amino acid sequence of glucagon was described in the late-1950s. Year 1950 ( MCML) was a Common year starting on Sunday (link will display the full calendar of the Gregorian calendar. [2] A more complete understanding of its role in physiology and disease was not established until the 1970s, when a specific radioimmunoassay was developed. Year 1970 ( MCMLXX) was a Common year starting on Thursday (link shows full calendar of the Gregorian calendar. Radioimmunoassay (RIA is a Scientific method used to test Antigens (for example Hormone levels in the Blood) without the need to use a
Structure
Glucagon is a 29-amino acid polypeptide. In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino Its primary structure in humans is: NH2-His-Ser-Gln-Gly-Thr-Phe- Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser- Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu- Met-Asn-Thr-COOH. In Biochemistry, the primary structure of a biological molecule is the exact specification of its atomic composition and the chemical bonds connecting those atoms (including Amines are Organic compounds and Functional groups that contain a basic Nitrogen Atom with a Lone pair. Histidine (abbreviated as His or H) is one of the 20 standard Amino acids present in Proteins In the Nutritional sense in Serine (abbreviated as Ser or S) is an Organic compound with the formula H[[oxygen O]]2 CCH NH sub>2CH2OH Glutamine (abbreviated as Gln or Q; the abbreviation Glx or Z represents either glutamate or Glutamic acid) is one of the 20 Glycine (abbreviated as Gly or G) is the Organic compound with the formula NH2CH2COOH Threonine (abbreviated as Thr or T) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH(OHCH3 Phe redirects here For the BitTorrent feature see PHE. For the constellation see Phoenix (constellation. Threonine (abbreviated as Thr or T) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH(OHCH3 Serine (abbreviated as Ser or S) is an Organic compound with the formula H[[oxygen O]]2 CCH NH sub>2CH2OH Aspartic acid (abbreviated as Asp or D; Asx or B represent either aspartic acid or Asparagine) is an α- Amino acid Tyrosine (abbreviated as Tyr or Y) or 4-hydroxyphenylalanine, is one of the 20 Amino acids that are used by cells to synthesize Serine (abbreviated as Ser or S) is an Organic compound with the formula H[[oxygen O]]2 CCH NH sub>2CH2OH Lysine (abbreviated as Lys or K) is an α- Amino acid with the Chemical formula HO2CCH(NH2(CH24NH2 Tyrosine (abbreviated as Tyr or Y) or 4-hydroxyphenylalanine, is one of the 20 Amino acids that are used by cells to synthesize Leucine (abbreviated as Leu or L) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH2CH(CH32 Aspartic acid (abbreviated as Asp or D; Asx or B represent either aspartic acid or Asparagine) is an α- Amino acid Serine (abbreviated as Ser or S) is an Organic compound with the formula H[[oxygen O]]2 CCH NH sub>2CH2OH Arginine (abbreviated as Arg or R) is an α- Amino acid. The L-form is one of the 20 most common natural amino acids Arginine (abbreviated as Arg or R) is an α- Amino acid. The L-form is one of the 20 most common natural amino acids Alanine (abbreviated as Ala or A) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH3 Glutamine (abbreviated as Gln or Q; the abbreviation Glx or Z represents either glutamate or Glutamic acid) is one of the 20 Aspartic acid (abbreviated as Asp or D; Asx or B represent either aspartic acid or Asparagine) is an α- Amino acid Phe redirects here For the BitTorrent feature see PHE. For the constellation see Phoenix (constellation. Valine (abbreviated as Val or V) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH(CH32 Glutamine (abbreviated as Gln or Q; the abbreviation Glx or Z represents either glutamate or Glutamic acid) is one of the 20 Tryptophan (abbreviated as Trp or W) is one of the 20 standard amino acids, as well as an Essential amino acid in the Human diet Leucine (abbreviated as Leu or L) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH2CH(CH32 Methionine ( abbreviated as Met or M) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH2CH2SCH3 Asparagine (abbreviated as Asn or N; Asx or B represent either asparagine or Aspartic acid) is one of the 20 most common natural Threonine (abbreviated as Thr or T) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH(OHCH3 Carboxyl group or CO2H is a Functional group present in Amino acids and Carboxylic acids Its structure is composed of one carbon atom attached
The polypeptide has a molecular weight of 3485 daltons. The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one The unified atomic mass unit ( u) or Dalton ( Da) or sometimes universal mass unit, is an unit of Mass used to express
Physiology
Production
The hormone is synthesized and secreted from alpha cells (α-cells) of the islets of Langerhans, which are located in the endocrine portion of the pancreas. Alpha cells are endocrine cells in the Islets of Langerhans of the Pancreas. Islets of Langerhans is the area in which the Endocrine (ie hormone-producing cells of the Pancreas are grouped In rodents, the alpha cells are located in the outer rim of the islet. Human islet structure is much less segregated, and alpha cells are distributed throughout the islet.
Regulatory mechanism
Increased secretion of glucagon is caused by:
- Decreased plasma glucose
- Increased catecholamines - norepinephrine and epinephrine
- Increased plasma amino acids (to protect from hypoglycemia if an all protein meal is consumed)
- Sympathetic nervous system
- Acetylcholine
- Cholecystokinin
Decreased secretion of glucagon (inhibition) is caused by:
Function
Glucagon helps maintain the level of glucose in the blood by binding to glucagon receptors on hepatocytes, causing the liver to release glucose - stored in the form of glycogen - through a process known as glycogenolysis. Blood sugar, used in a physiological context is a misnomer and misleading Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood The Sympathetic Nervous System ( SNS) is a branch of the Autonomic nervous system along with the Enteric nervous system and Parasympathetic nervous The Chemical compound acetylcholine (often abbreviated ACh) is a Neurotransmitter in both the Peripheral nervous system (PNS and Central Cholecystokinin ( CCK; from Greek chole, "bile" cysto, "sac" kinin, "move" hence move the bile-sac Somatostatin (also known as growth hormone inhibiting hormone ( GHIH) or somatotropin release-inhibiting factor ( SRIF) is a Peptide hormone Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells such as nutrients and oxygen—and transports Waste products The glucagon receptor is a 62 KDa Peptide that is activated by Glucagon and is a member of the G-protein coupled family of receptors coupled Hepatocytes make up 70-80% of the Cytoplasmic mass of the Liver. The liver is a vital organ in the human body and is present in Vertebrates and some other animals Glycogen is a Polysaccharide of Glucose (Glc which functions as the secondary short term energy storage in Animal cells Glycogenolysis (also known as "Glycogenlysis" is the Catabolism of Glycogen by removal of a Glucose monomer through cleavage with inorganic As these stores become depleted, glucagon then encourages the liver to synthesize additional glucose by gluconeogenesis. Gluconeogenesis (abreviated GNG) is a Metabolic pathway that results in the generation of Glucose from non- Carbohydrate carbon substrates such This glucose is released into the bloodstream. Both of these mechanisms lead to glucose release by the liver, preventing the development of hypoglycemia. Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood Glucagon also regulates the rate of glucose production through lipolysis. Lipolysis is the breakdown of fat stored in fat cells During this process Free fatty acids are released into the bloodstream and circulate throughout the body
- Increased free fatty acids and ketoacids into the blood
- Increased urea production
Mechanism of action
Glucagon binds to the glucagon receptor, a G protein-coupled receptor located in the plasma membrane. In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which Keto acids are organic Acids containing a Ketone Functional group and a Carboxylic acid group Urea is an Organic compound with the Chemical formula ( N[[hydrogen H]]22 C[[oxygen O]] The glucagon receptor is a 62 KDa Peptide that is activated by Glucagon and is a member of the G-protein coupled family of receptors coupled G protein-coupled receptors ( GPCRs) also known as seven transmembrane domain receptors, 7TM receptors, heptahelical receptors, and The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer The conformation change in the receptor activates G proteins, a heterotrimeric protein with α, β, and γ subunits. GTP chemical structurepng|thumb|180px| Guanosine triphosphate]] G proteins short for guanine nucleotide-binding proteins, are a family of Proteins involved The subunits breakup as a result of substitution of a GDP molecule with a GTP mol, and the alpha subunit specifically activates the next enzyme in the cascade, adenylate cyclase. Adenylate cyclase ( also known as adenylyl cyclase or AC) is a Lyase Enzyme.
Adenylate cyclase manufactures cAMP (cyclical AMP) which activates protein kinase A (cAMP-dependent protein kinase). In Cell biology, protein kinase A, refers to a family of Enzymes whose activity is dependent on the level of Cyclic AMP (cAMP in the cell This enzyme in turn activates phosphorylase kinase, which in turn, phosphorylates glycogen phosphorylase, converting into the active form called phosphorylase A. Phosphorylase kinase is a Serine/threonine-specific protein kinase which converts Glycogen phosphorylase b to glycogen phosphorylase a activating it to release Glycogen phosphorylase is one of the Phosphorylase Enzymes ( It breaks up Glycogen into Glucose Subunits. Phosphorylase A is the enzyme responsible for the release of glucose-1-phosphate from glycogen polymers. Glucose 1-phosphate (also called cori ester) is a Glucose molecule with a Phosphate group on the 1'-carbon Glycogen is a Polysaccharide of Glucose (Glc which functions as the secondary short term energy storage in Animal cells
Pathology
Abnormally-elevated levels of glucagon may be caused by pancreatic tumors such as glucagonoma, symptoms of which include necrolytic migratory erythema (NME), elevated amino acids and hyperglycemia. See also Cancer A tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells (termed neoplastic A glucagonoma is a rare Tumor of the Alpha cells of the Pancreas that results in up to a 1000-fold overproduction of the Hormone Glucagon Necrolytic migratory erythema (NME is a classical symptom observed in patients with Glucagonoma and is present in 80% of cases Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an excessive amount of Glucose circulates in the Blood plasma It may occur alone or in the context of multiple endocrine neoplasia type 1. Multiple endocrine neoplasia type 1 or Werner syndrome is part of a group of disorders that affect the Endocrine system.
Uses
An injectable form of glucagon is vital first aid in cases of severe hypoglycemia when the victim is unconscious or for other reasons cannot take glucose orally. Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood The dose for an adult is typically 1 milligram, and the glucagon is given by intramuscular, intravenous or subcutaneous injection, and quickly raises blood glucose levels. Blood sugar, used in a physiological context is a misnomer and misleading Glucagon can also be administered intravenously at 0. 25 - 0. 5 unit.
Anecdotal evidence suggests a benefit of higher doses of glucagon in the treatment of overdose with beta blockers; the likely mechanism of action is the increase of cAMP in the myocardium, effectively bypassing the inhibitory action of the β-adrenergic second messenger system. Beta blockers (sometimes written as β-blocker) are a class of drugs used for various indications but particularly for the management of Cardiac arrhythmias Myocardium is the muscular tissue of the Heart. Relationship to other layers The other tissues of the heart are the Endocardium The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the Catecholamines Adrenergic receptors In Cell physiology, a secondary messenger system (also known as a second messenger system) is a method of cellular signaling whereby a diffusable signaling molecule [3]
Glucagon acts very quickly: common side effects include headache and nausea.
Drug interactions: Glucagon interacts only with oral anticoagulants increasing the tendency to bleed.
Media
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Glucagon stereogram
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References in pop culture
- American parodist "Weird Al" Yankovic released a song entitled Pancreas on his album Straight Outta Lynwood, which uses the lyric "Insulin, Glucagon, flowing from the Islets of Langerhans" as a repeated catchy chorus in the final minute of the song. A parody (ˈpɛɹədiː US, [ˈpaɹədiː] UK) in contemporary usage is a work created to mock comment on or poke fun at an original work its subject Alfred Matthew "Weird Al" Yankovic (ˈjæŋkəvɪk born October 23 1959 is a Grammy Award winning American singer Musician, actor satirist The pancreas is a Gland organ in the digestive and Endocrine system of Vertebrates. Straight Outta Lynwood is the twelfth album by "Weird Al" Yankovic. Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance Islets of Langerhans is the area in which the Endocrine (ie hormone-producing cells of the Pancreas are grouped
References
- ^ Kimball C, Murlin J. Aqueous extracts of pancreas III. Some precipitation reactions of insulin. J Biol Chem 1923;58:337-348. PDF fulltext.
- ^ Bromer W, Winn L, Behrens O. The amino acid sequence of glucagon V. Location of amide groups, acid degradation studies and summary of sequential evidence. J Am Chem Soc 1957;79:2807-2810.
- ^ White CM. A review of potential cardiovascular uses of intravenous glucagon administration. J Clin Pharmacol 1999;39:442-7. PMID 10234590.
Further reading
- Kieffer TJ, Habener JF (2000). "The glucagon-like peptides. ". Endocr. Rev. 20 (6): 876-913. PMID 10605628.
- Drucker DJ (2003). "Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. ". Mol. Endocrinol. 17 (2): 161-71. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12554744.
- Jeppesen PB (2004). "Clinical significance of GLP-2 in short-bowel syndrome. ". J. Nutr. 133 (11): 3721-4. PMID 14608103.
- Brubaker PL, Anini Y (2004). "Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2. ". Can. J. Physiol. Pharmacol. 81 (11): 1005-12. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 14719035.
- Baggio LL, Drucker DJ (2005). "Clinical endocrinology and metabolism. Glucagon-like peptide-1 and glucagon-like peptide-2. ". Best Pract. Res. Clin. Endocrinol. Metab. 18 (4): 531-54. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15533774.
- Holz GG, Chepurny OG (2006). "Diabetes outfoxed by GLP-1?". Sci. STKE 2005 (268): pe2. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15671479.
- Dunning BE, Foley JE, Ahrén B (2006). "Alpha cell function in health and disease: influence of glucagon-like peptide-1. ". Diabetologia 48 (9): 1700-13. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16132964.
- Gautier JF, Fetita S, Sobngwi E, Salaün-Martin C (2005). "Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. ". Diabetes Metab. 31 (3 Pt 1): 233-42. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16142014.
- De León DD, Crutchlow MF, Ham JY, Stoffers DA (2006). "Role of glucagon-like peptide-1 in the pathogenesis and treatment of diabetes mellitus. ". Int. J. Biochem. Cell Biol. 38 (5-6): 845-59. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16202636.
- Beglinger C, Degen L (2007). "Gastrointestinal satiety signals in humans--physiologic roles for GLP-1 and PYY?". Physiol. Behav. 89 (4): 460-4. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16828127.
- Stephens JW, Bain SC (2007). "Safety and adverse effects associated with GLP-1 analogues. ". Expert opinion on drug safety 6 (4): 417-22. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17688385.
- Orskov C, Bersani M, Johnsen AH, et al. (1989). "Complete sequences of glucagon-like peptide-1 from human and pig small intestine. ". J. Biol. Chem. 264 (22): 12826-9. PMID 2753890.
- Drucker DJ, Asa S (1988). "Glucagon gene expression in vertebrate brain. ". J. Biol. Chem. 263 (27): 13475-8. PMID 2901414.
- Novak U, Wilks A, Buell G, McEwen S (1987). "Identical mRNA for preproglucagon in pancreas and gut. ". Eur. J. Biochem. 164 (3): 553-8. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 3569278.
- White JW, Saunders GF (1986). "Structure of the human glucagon gene. ". Nucleic Acids Res. 14 (12): 4719-30. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 3725587.
- Schroeder WT, Lopez LC, Harper ME, Saunders GF (1984). "Localization of the human glucagon gene (GCG) to chromosome segment 2q36----37. ". Cytogenet. Cell Genet. 38 (1): 76-9. PMID 6546710.
- Bell GI, Sanchez-Pescador R, Laybourn PJ, Najarian RC (1983). "Exon duplication and divergence in the human preproglucagon gene. ". Nature 304 (5924): 368-71. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 6877358.
- Kärgel HJ, Dettmer R, Etzold G, et al. (1982). "Action of rat liver cathepsin L on glucagon. ". Acta Biol. Med. Ger. 40 (9): 1139-43. PMID 7340337.
- Wayman GA, Impey S, Wu Z, et al. (1994). "Synergistic activation of the type I adenylyl cyclase by Ca2+ and Gs-coupled receptors in vivo. ". J. Biol. Chem. 269 (41): 25400-5. PMID 7929237.
- Unson CG, Macdonald D, Merrifield RB (1993). "The role of histidine-1 in glucagon action. ". Arch. Biochem. Biophys. 300 (2): 747-50. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 8382034.
See also
Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Proglucagon is a precursor of Glucagon, and several other components Islets of Langerhans is the area in which the Endocrine (ie hormone-producing cells of the Pancreas are grouped The pancreas is a Gland organ in the digestive and Endocrine system of Vertebrates.Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic