[[Image:Glucagon.png|thumb|right|200px|Glucagon ball and stick model, with the [[carboxyl]] terminus above and the [[amino]] terminus below]]
[[Image:Glucagon_rednblue.png|thumb|right|200px|A microscopic image stained for glucagon.]]
|fdaLIADAdult=
{{CMG}}
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
* Dosing Information
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=====Condition3=====
* Dosing Information
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* Dosing Information
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=====Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport=
=====Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Contraindications-->
|contraindications=
* Condition1
<!--Warnings-->
|warnings=
* Description
====Precautions====
* Description
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
|clinicalTrials=
There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=
There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Drug Interactions-->
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* Drug
:* Description
<!--Use in Specific Populations-->
|useInPregnancyFDA=
* '''Pregnancy Category'''
|useInPregnancyAUS=
* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=
There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=
There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInPed=
There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=
There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=
There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=
There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
|administration=
* Oral
* Intravenous
|monitoring=
There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
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<!--IV Compatibility-->
|IVCompat=
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<!--Overdosage-->
|overdose=
===Acute Overdose===
====Signs and Symptoms====
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====Management====
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===Chronic Overdose===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
<!--Pharmacology-->
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<!--Mechanism of Action-->
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*
<!--Structure-->
|structure=
*
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
<!--Pharmacodynamics-->
|PD=
There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
<!--Pharmacokinetics-->
|PK=
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<!--Clinical Studies-->
|clinicalStudies=
There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
<!--How Supplied-->
|howSupplied=
*
==Overview==
<!--Patient Counseling Information-->
'''Glucagon''' is an important [[hormone]] involved in [[carbohydrate metabolism]]. 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 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.
== History ==
|fdaPatientInfo=
In the 1920s, Kimball and Murlin studied [[pancreas|pancreatic]] extracts and found an additional substance with [[hyperglycemia|hyperglycemic]] properties. They described glucagon in 1923.<ref>Kimball C, Murlin J. Aqueous extracts of pancreas III. Some precipitation reactions of insulin. ''J Biol Chem'' 1923;58:337-348. [http://www.jbc.org/cgi/reprint/58/1/337 PDF fulltext].</ref> The amino acid sequence of glucagon was described in the late-1950s.<ref>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.</ref> A more complete understanding of its role in physiology and disease was not established until the 1970s, when a specific [[radioimmunoassay]] was developed.
==Structure==
There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
Glucagon is a 29-[[amino acid]] [[polypeptide]]. Its [[primary structure]] in humans is: [[amine|NH<sub>2</sub>]]-[[Histidine|His]]-[[Serine|Ser]]-[[Glutamine|Gln]]-[[Glycine|Gly]]-[[Threonine|Thr]]-[[Phenylalanine|Phe]]-
The polypeptide has a [[molecular weight]] of 3485 [[Atomic mass unit|dalton]]s.
<!--Precautions with Alcohol-->
==Physiology==
|alcohol=
===Production===
The hormone is synthesized and secreted from [[alpha cell]]s (α-cells) of the [[islets of Langerhans]], which are located in the endocrine portion of the pancreas. 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===
* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
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:
<!--Brand Names-->
* [[Somatostatin]]
* [[Insulin]]
===Function===
|brandNames=
Glucagon helps maintain the level of [[glucose]] in the [[blood]] by binding to [[glucagon receptor]]s on [[hepatocyte]]s, causing the [[liver]] to release glucose - stored in the form of [[glycogen]] - through a process known as [[glycogenolysis]]. As these stores become depleted, glucagon then encourages the liver to synthesize additional glucose by [[gluconeogenesis]]. This glucose is released into the bloodstream. Both of these mechanisms lead to glucose release by the liver, preventing the development of [[hypoglycemia]].
Glucagon also regulates the rate of glucose production through [[lipolysis]].
* Increased free [[fatty acids]] and [[ketoacids]] into the blood
* ®<ref>{{Cite web | title = | url = }}</ref>
* Increased [[urea]] production
===Mechanism of action===
<!--Look-Alike Drug Names-->
Glucagon binds to the [[glucagon receptor]], a [[G protein-coupled receptor]] located in the [[plasma membrane]]. The conformation change in the receptor activates [[G protein]]s, a heterotrimeric protein with α, β, and γ subunits. The subunits breakup under GTP hydrolysis and the alpha subunit specifically activates the next enzyme in the cascade, [[adenylate cyclase]].
Adenylate cyclase manufactures [[cAMP]] (cyclical AMP) which activates [[protein kinase A]] (cAMP-dependent protein kinase). This enzyme in turn activates [[phosphorylase B kinase]], which in turn, phosphorylates [[phosphorylase B]], converting into the active form called phosphorylase A. Phosphorylase A is the enzyme responsible for the release of [[glucose-1-phosphate]] from [[glycogen]] polymers.
|lookAlike=
==Pathology==
* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
Abnormally-elevated levels of glucagon may be caused by pancreatic [[tumor]]s such as [[glucagonoma]], symptoms of which include [[necrolytic migratory erythema]] (NME), elevated amino acids and [[hyperglycemia]]. It may occur alone or in the context of [[multiple endocrine neoplasia type 1]].
==Uses==
<!--Drug Shortage Status-->
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. 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. 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 blocker]]s; the likely mechanism of action is the increase of cAMP in the [[myocardium]], effectively bypassing the inhibitory action of the [[Adrenergic receptor|β-adrenergic]] [[second messenger system]].<ref>White CM. A review of potential cardiovascular uses of intravenous glucagon administration. ''J Clin Pharmacol'' 1999;39:442-7. PMID 10234590.</ref>
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Glucagon acts very quickly: common side effects include headache and nausea.
<!--Pill Image-->
Drug interactions: Glucagon interacts only with oral anticoagulants increasing the tendency to bleed.
{{PillImage
==Media==
|fileName=No image.jpg|This image is provided by the National Library of Medicine.
*{{cite journal | author=Dunning BE, Foley JE, Ahrén B |title=Alpha cell function in health and disease: influence of glucagon-like peptide-1. |journal=Diabetologia |volume=48 |issue= 9 |pages= 1700-13 |year= 2006 |pmid= 16132964 |doi= 10.1007/s00125-005-1878-0 }}
*{{cite journal | author=Gautier JF, Fetita S, Sobngwi E, Salaün-Martin C |title=Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. |journal=Diabetes Metab. |volume=31 |issue= 3 Pt 1 |pages= 233-42 |year= 2005 |pmid= 16142014 |doi= | doi=10.1016/S1262-3636(07)70190-8}}
*{{cite journal | author=De León DD, Crutchlow MF, Ham JY, Stoffers DA |title=Role of glucagon-like peptide-1 in the pathogenesis and treatment of diabetes mellitus. |journal=Int. J. Biochem. Cell Biol. |volume=38 |issue= 5-6 |pages= 845-59 |year= 2006 |pmid= 16202636 |doi= 10.1016/j.biocel.2005.07.011 }}
*{{cite journal | author=Beglinger C, Degen L |title=Gastrointestinal satiety signals in humans--physiologic roles for GLP-1 and PYY? |journal=Physiol. Behav. |volume=89 |issue= 4 |pages= 460-4 |year= 2007 |pmid= 16828127 |doi= 10.1016/j.physbeh.2006.05.048 }}
*{{cite journal | author=Stephens JW, Bain SC |title=Safety and adverse effects associated with GLP-1 analogues. |journal=Expert opinion on drug safety |volume=6 |issue= 4 |pages= 417-22 |year= 2007 |pmid= 17688385 |doi= 10.1517/14740338.6.4.417 }}
*{{cite journal | author=Orskov C, Bersani M, Johnsen AH, ''et al.'' |title=Complete sequences of glucagon-like peptide-1 from human and pig small intestine. |journal=J. Biol. Chem. |volume=264 |issue= 22 |pages= 12826-9 |year= 1989 |pmid= 2753890 |doi= }}
*{{cite journal | author=Novak U, Wilks A, Buell G, McEwen S |title=Identical mRNA for preproglucagon in pancreas and gut. |journal=Eur. J. Biochem. |volume=164 |issue= 3 |pages= 553-8 |year= 1987 |pmid= 3569278 |doi= | doi=10.1111/j.1432-1033.1987.tb11162.x}}
*{{cite journal | author=White JW, Saunders GF |title=Structure of the human glucagon gene. |journal=Nucleic Acids Res. |volume=14 |issue= 12 |pages= 4719-30 |year= 1986 |pmid= 3725587 |doi= | doi=10.1093/nar/14.12.4719}}
*{{cite journal | author=Schroeder WT, Lopez LC, Harper ME, Saunders GF |title=Localization of the human glucagon gene (GCG) to chromosome segment 2q36----37. |journal=Cytogenet. Cell Genet. |volume=38 |issue= 1 |pages= 76-9 |year= 1984 |pmid= 6546710 |doi= }}
*{{cite journal | author=Bell GI, Sanchez-Pescador R, Laybourn PJ, Najarian RC |title=Exon duplication and divergence in the human preproglucagon gene. |journal=Nature |volume=304 |issue= 5924 |pages= 368-71 |year= 1983 |pmid= 6877358 |doi= | doi=10.1038/304368a0}}
*{{cite journal | author=Kärgel HJ, Dettmer R, Etzold G, ''et al.'' |title=Action of rat liver cathepsin L on glucagon. |journal=Acta Biol. Med. Ger. |volume=40 |issue= 9 |pages= 1139-43 |year= 1982 |pmid= 7340337 |doi= }}
*{{cite journal | author=Wayman GA, Impey S, Wu Z, ''et al.'' |title=Synergistic activation of the type I adenylyl cyclase by Ca2+ and Gs-coupled receptors in vivo. |journal=J. Biol. Chem. |volume=269 |issue= 41 |pages= 25400-5 |year= 1994 |pmid= 7929237 |doi= }}
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Black Box Warning
Title
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Overview
Glucagon is a that is FDA approved for the {{{indicationType}}} of . There is a Black Box Warning for this drug as shown here. Common adverse reactions include .
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Condition1
Dosing Information
Dosage
Condition2
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Condition3
Dosing Information
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Condition4
Dosing Information
Dosage
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Glucagon in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Glucagon in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Glucagon in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Glucagon in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Glucagon in pediatric patients.
Contraindications
Condition1
Warnings
Title
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Description
Precautions
Description
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Glucagon in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Glucagon in the drug label.
