Grelin

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GHRL
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1P7X,%%s2JSH, 2JSI, 2JSJ

Identifikatori
AliasiGHRL
Vanjski ID-jeviOMIM: 605353 MGI: 1930008 HomoloGene: 9487 GeneCards: GHRL
Lokacija gena (čovjek)
Hromosom 3 (čovjek)
Hrom.Hromosom 3 (čovjek)[1]
Hromosom 3 (čovjek)
Genomska lokacija za GHRL
Genomska lokacija za GHRL
Bend3p25.3Početak10,285,666 bp[1]
Kraj10,292,947 bp[1]
Lokacija gena (miš)
Hromosom 6 (miš)
Hrom.Hromosom 6 (miš)[2]
Hromosom 6 (miš)
Genomska lokacija za GHRL
Genomska lokacija za GHRL
Bend6 E3|6 52.84 cMPočetak113,716,119 bp[2]
Kraj113,719,880 bp[2]
Ontologija gena
Molekularna funkcija protein tyrosine kinase activator activity
hormone activity
GO:0001948 protein binding
ghrelin receptor binding
G protein-coupled receptor binding
growth hormone-releasing hormone activity
Ćelijska komponenta postsynapse
citoplazma
endoplasmic reticulum lumen
extracellular region
Akson
secretory granule lumen
Vanćelijsko
Schaffer collateral - CA1 synapse
glutamatergic synapse
Biološki proces positive regulation of appetite
G protein-coupled receptor signaling pathway
positive regulation of cortisol secretion
positive regulation of growth hormone receptor signaling pathway
negative regulation of insulin secretion
gastric acid secretion
positive regulation of cytosolic calcium ion concentration
dendrite development
regulation of response to food
negative regulation of apoptotic process
positive regulation of corticotropin secretion
negative regulation of locomotion
cortisol secretion
response to estrogen
negative regulation of endothelial cell proliferation
positive regulation of circadian sleep/wake cycle, non-REM sleep
cartilage development
activation of MAPK activity
decidualization
regulation of cell population proliferation
growth hormone secretion
positive regulation of growth hormone secretion
excitatory postsynaptic potential
hormone-mediated signaling pathway
glucose metabolic process
positive regulation of multicellular organism growth
negative regulation of angiogenesis
response to hormone
actin polymerization or depolymerization
positive regulation of response to food
negative regulation of circadian sleep/wake cycle, REM sleep
negative regulation of inflammatory response
positive regulation of insulin secretion
positive regulation of synapse assembly
positive regulation of protein tyrosine kinase activity
adult feeding behavior
response to nutrient levels
positive regulation of eating behavior
positive regulation of adipose tissue development
negative regulation of interleukin-1 beta production
gastric emptying
positive regulation of insulin secretion involved in cellular response to glucose stimulus
positive regulation of growth
response to electrical stimulus
regulation of transmission of nerve impulse
positive regulation of bone development
positive regulation of sprouting angiogenesis
positive regulation of gastro-intestinal system smooth muscle contraction
positive regulation of small intestine smooth muscle contraction
regulation of gastric motility
positive regulation of vascular endothelial cell proliferation
positive regulation of growth rate
positive regulation of small intestinal transit
positive regulation of gastric mucosal blood circulation
positive regulation of feeding behavior
regulation of signaling receptor activity
energy homeostasis
postsynaptic modulation of chemical synaptic transmission
regulation of postsynapse organization
positive regulation of cold-induced thermogenesis
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)
NM_001134941
NM_001134944
NM_001134945
NM_001134946
NM_001302821

NM_001302822
NM_001302823
NM_001302824
NM_001302825
NM_016362

NM_021488
NM_001286404
NM_001286405
NM_001286406
NM_001379129

RefSeq (bjelančevina)
NP_001128413
NP_001128416
NP_001128417
NP_001128418
NP_001289750

NP_001289751
NP_001289752
NP_001289753
NP_001289754
NP_057446
NP_001128413
NP_001128416
NP_001128417
NP_001128418
NP_001289750
NP_001289751
NP_001289752
NP_001289753
NP_001289754
NP_057446

NP_001273333
NP_001273334
NP_001273335
NP_067463
NP_001366058

Lokacija (UCSC)Chr 3: 10.29 – 10.29 MbChr 6: 113.72 – 113.72 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Grelin ili lenomorelin, INN, je cirkulirajući hormon kojeg proizvode enteroendokrine ćelije gastrointestinalnog trakta, posebno želudac,[5][6] a često se naziva "hormonom gladi" jer povećava unos hrane.[6] Razina grelina u krvi je najviša prije obroka kada je osoba gladna, a na niži nivo vraća se nakon obroka.[6][7] Grelin također može pomoći i u pripremi za unos hrane,[6][8] povećanjem želučanog motiliteta i lučenja želučane kiseline.[6]

Grelin aktivira ćelije u prednjem režnju hipofize i hipotalamusno lučno jezgro,[6][9] uključujući neurone neuropeptida Y koji podstiču apetit.[6][10] Grelin stimulira moždane strukture koje imaju receptorsekretagog receptor 1A (GHSR - 1A) hormona rasta.[6][11] Također učestvuje u regulaciji spoznaja nagrade,[12] učenja i pamćenja i tciklusa spavanje-buđenje, osjećanja okusa, ponašanje nagrađivanja i metabolizam glukoze.[6][13][14]

Historija i ime[uredi | uredi izvor]

Grelin je otkriven nakon što je receptor za grelin (nazvan receptor za sekretagog hormona rasta tipa 1A ili GHS-R) određen 1999.[6] Naziv hormona zasnovan je na njegovoj ulozi: growth hormone -releasing peptid, s pozivom na korijen protoindoevropska rekonstrukcija/ gʰreh₁-| gʰre– , što znači rasti.[6]

Struktura grelina

Gen, transkripcijjski proizvod i struktura[uredi | uredi izvor]

Preprogrelin (zeleno i plavo) i grelin (zeleno).

Gen GHRL proizvodi iRNK sa četiri egzona. Translacijom i preradom, nastaje pet proizvoda: prvi je "preprogrelin" sa 117 aminokiselina. (Homologan je promotilinu; oba su članovi porodice motilina. Cijepa se da bi se dobGhrelina.jpgio progrelin, koji se također cijepa da bi se dobio 28-aminokiselinski (necilirani) grelin i C-grelin. Pretpostavlja se da je obestatin odcijepljen od C-grelina.[15]

Grelin postaje aktivan samo kada je kaprilna kiselina kaprilna (oktanska) kiselina posttranslacijski povezan sa serinom enzima grelin O-aciltransferaza (GOAT), u 3-položaju. Nalazi se na ćelijskoj membrani grelinskih ćelija u želucu i pankreasu.[16] Neoktanoilirani oblik je dezacil grelin. Ne aktivira GHS-R receptor, ali ima druge efekte: srčani,[17] antigrelin,[18] appetite stimulation,[19] i inhibicija izlaska glukoze iz jetre.[20] Također su uočeni bočni lanci koji nisu oktanoil: i oni mogu pokrenuti receptor za grelin.[21] Konkretno, utvrđeno je da dekanoil grelin čini značajan dio grelina u opticaju kod miševa, ali od 2011. njegovo prisustvo kod ljudi nije utvrđeno.[22]

Grelinske ćelije[uredi | uredi izvor]

Alternativni nazivi[uredi | uredi izvor]

Grelinska ćelija je poznata i kao A-likolika ćelija (gušterača), X-ćelija (zbog nepoznate funkcije), X / A-likolika ćelija (pacovi), epsilon ćelija (gušterača), P/D sub 1 ćelija (ljudi) i Gr ćelija (skraćenica od grelinska ćelija).[23]

Lokacija[uredi | uredi izvor]

Grelin ćelije nalaze se uglavnom u želucu [24] i dvanaestpalačnom crijevu, ali također i u jejunumu, plućima i gušteračinim otočićima,[25] gonadama, kori nadbubrežne žlijezde, placenti i bubrezima. Također se pokazalo da se mjestimično luči i u mozgu.[26]

Obilježja[uredi | uredi izvor]

Grelinske ćelije se nalaze u oksintskim žlijezdama (20% ćelija),[27] piloričnim žlijezdama i tankom crijevu. To su jajolike ćelije sa zrncima (granulama).[28] They have gastrin receptors.[29] Neke proizvode nesfatin-1.[30] Grelinske ćelije se na kraju diferenciraju u gušterači: one su progenitorne ćelije koje tamo mogu stvoriti A-ćelije, PP ćelije i Beta-ćelije.[31]

Funkcija i mehanizam djelovanja[uredi | uredi izvor]

Grelin je sudionik u regulaciji složenog procesa energetske homeostaze koji prilagođava i unos energije – podešavanjem signala gladi – i izlaz energije, podešavanjem udjela energije koja ide u proizvodnju ATP , skladištenje masti, glikogena i kratkoročni gubitak toplote. Neto rezultat ovih procesa ogleda se u tjelesnoj težini i pod stalnim je nadzorom i prilagođavanjem, na osnovu metaboličkih signala i potreba. U bilo kojem trenutku, može biti u ravnoteži ili neravnoteži. Komunikacija želudacmozak, važan je dio energetske homeostaze i vjerovatno je nekoliko komunikacijskih putova, uključujući želučani unutarćelijski put S6K1 posredovanja interakcije grelina, nesfatina i endokannabinoida želučanid sistema [32] i uzlaznih (aferentnih) i silaznih (eferentnih) vagusnih sigmala.

Grelini i njihve sintetske zamjene (sekretagog hormona rasta povećavaju tjelesnu težinu i masnu masu[33][34][35] ciljajući receptore u the lučnom jezgru[9] koji uključuju neuronski neuropeptid Y (NPY) i agouti-srodni protein (AgRP).[10][36] Ovi neuroni reagirauju na grelin i osetljivi su i na leptin i na insulin.[37] Grelin smanjuje osjetljivost želučanih vagus nih uzlaznih nervnih vlakana, tako da su manje osjetljiva na rastezanje želuca.[38]

Pored svoje funkcije u energetskoj homeostazi, grelin također aktivira holinergijsko-dopaminergijsku nagradnu vezu u ulazima u ventralno tegmentno područje i u mezolimbni put ,[39] krug koji komunicira hedonske i ojačavajuće aspekte prirodnih nagrada,[13] such as food and addictive drugs such as ethanol.[37][40][41] Grelinski receptori nalaze se u neuronima tog kruga.[12][13] Za osjećaj nagrade od alkohola, potrebna je signalizacija hipotalamusnog grelina[42] i ukusna / korisna hrana.[43][44]

Grelin je povezan s izazivanjem apetita i ponašanjem u prehrani. Razina grelina u cirkulaciji je najviša neposredno prije obroka, a najniža neposredno nakon objedovanja.[45][46] Pokazalo se da injekcije grelina kod ljudi i pacova povećavaju unos hrane na način koji ovisi o dozi.[47] Dakle, što se više ubrizga grelina, to se više konzumira. Međutim, grelin ne povećava veličinu obroka, već samo njihov broj.[48] Injekcije grelina također povećavaju motivaciju životinje da traži hranu, ponašanja koja uključuju pojačano njuškanje, traženje hrane i gomilanje hrane. Tjelesna težina regulira se energetskom ravnotežom, količinom energije koja se uzima u odnosu na količinu energije koja se troši tokom dužeg vremenskog perioda. Studije su pokazale da su nivoi grelina u negativnoj korelaciji sa težinom. Ovi podaci sugeriraju da grelin funkcionira kao signal gojaznosti, glasnik između tjelesnih zaliha energije i mozga.[8]

Razine u krvi[uredi | uredi izvor]

Nivoi u krvi su u opsegu pmol/l. Mogu se izmjeriti i aktivni i ukupni grelin.[49] Koncentracije grelina u cirkulaciji rastu prije jela i padaju nakon toga,[45] snažnije kao odgovor na proteine i ugljikohidrate nego na lipide..[22]

Grelinski receptor[uredi | uredi izvor]

Grelinov receptor GHS-R1a (spojnica-varijanta receptor sekretagoga hormona rasta, pri čemu je spoj GHS-R1b neaktivan) uključen je u posredovanje bioloških efekata grelina širokog spektra, uključujući: stimulaciju oslobađanja hormona rasta, povećanje gladi, modulaciju metabolizma glukoze i lipida, regulaciju gastrointestinalnog motiliteta i sekrecije, zaštitu neuronskih i kardiovaskularnih ćelija i regulaciju imunske funkcije.[50] Prisutni su u velikoj gustoći u hipotalamusu i hipofizi, na vagusnom nervu (i na tijelima aferentnih ćelija i na eferentnim nervnim završecima) i u čitavom gastrointestinalnom traktu.[16][38]

Mjesto aktivnosti[uredi | uredi izvor]

Metabolizam glukoze[uredi | uredi izvor]

Čitav grelinski sistem (dAG, AG, GHS-R i GOAT) ima gluko-regulatorno djelovanje.[51]

Spavanje[uredi | uredi izvor]

Preliminarna istraživanja pokazuju da grelin sudjeluje u regulaciji cirkadijskih ritmova. Pregled je izvijestio da nije pronađen čvrst dokaz da je ograničenje sna uticalo na nivo grelina ili leptina ili na potrošnju energije.[52]

Reproductivni sistem[uredi | uredi izvor]

Grelin djeluje inhibitorno na sekreciju gonadotropin-oslobađajućeg hormona (GnRH). Može prouzrokovati smanjenu plodnost.[53]

Fetus i novorođenče[uredi | uredi izvor]

Grelin rano proizvode fetusna pluća i pospješuje njihov rast.[54] Razine grelina u krvi pupčane vrpce pokazuju korelaciju između nivoa grelina i porođajne težine.[49]

Anoreksija i gojaznost[uredi | uredi izvor]

Koncentracija grelina u plazmi gojaznih osoba niža je od one kod mršavijih osoba,[6][55] sugerirajući da grelin ne doprinosi pretilosti, osim u slučajevima Prader-Willijevim sindromom inducirane gojaznosti, gdje su visoke razine grelina u korelaciji s povećanim unosom hrane.[56][57] Osobe sa poremećsjrm zvanim anorexia nervosa imaju visok nivo grelina u plazmi[58] u poređenju sa vitkom i normalnom konstitucijom, kao kontrolom.[59][60] Razina grelina raste u doba dana od ponoći do zore kod mršavijih ljudi, što sugerira da postoji mahana u cirkadijskom ritmu gojaznih osoba.[61] Ghrelin levels are high in people with cancer-induced cachexia.[62] Nema dovoljno dokaza da bi se zaključilo bilo za ili protiv upotrebe grelina u liječenju kaheksije povezane s kancerom.[63]

Upravljanje bolestima[uredi | uredi izvor]

Operacija želučane premosnice[uredi | uredi izvor]

Operacija gastrične premosnice ne samo da smanjuje kapacitet crijeva za hranu, već i razinu grelina u usporedbi s mršavim ljudima i onima koji su mršavili dijetom.[6][64] Studije nisu razjasnile da li se razina grelina vraća u normalu kod ljudi koji su imali operaciju želučane premosnice nakon stabiliziranja gubitka kilograma.[65] Operacija gastričnog bajpasa, koja uključuje gastrektomija vertikalnih rukavaca, dugoročno smanjuje nivo grelina u plazmi za oko 60%.[66]

Također pogledajte[uredi | uredi izvor]

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000157017 - Ensembl, maj 2017
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