Grelin

Grelin ili lenomorelin, INN, je cirkulirajući hormon kojeg proizvode enteroendokrine ćelije gastrointestinalnog trakta, posebno želudac,[1][2] a često se naziva "hormonom gladi" jer povećava unos hrane.[2] Razina grelina u krvi je najviša prije obroka kada je osoba gladna, a na niži nivo vraća se nakon obroka.[2][3] Grelin također može pomoći i u pripremi za unos hrane,[2] [4] povećanjem želučanog motiliteta i lučenja želučane kiseline.[2]

Preprohormon grelin/obestatin
Ghrelin-3D-predicted.png
Identifikatori
Simbol GHRL
Entrez 51738
HUGO 18129
OMIM 605353
RefSeq NM_016362
UniProt Q9UBU3
Ostali podaci
Lokus Chr. 3 p25-26
Receptor povećanog lučenja hormona (GHS-R)
Identifikatori
Simbol GHSR
Entrez 2693
OMIM 601898
RefSeq NM_004122
UniProt Q92847
Ostali podaci
Lokus Chr. 3 q26.31
Ideogram human chromosome 3.svg
Kod čovjeka, genski lokus GHSR je nadugom (q) kraku hromosoma 3; pozicija za hormon 3p25-26; receptor: 3p26.31.

Grelin aktivira ćelije u prednjem režnju hipofize i hipotalamusno lučno jezgro,[2][5] uključujući neurone neuropeptida Y koji podstiču apetit.[2][6] Grelin stimulira moždane strukture koje imaju receptorsekretagog receptor 1A (GHSR - 1A) hormona rasta.[2][7] Također učestvuje u regulaciji spoznaja nagrade,[8] učenja i pamćenja i tciklusa spavanje-buđenje, osjećanja okusa, ponašanje nagrađivanja i metabolizam glukoze.[2][9][10]

Historija i imeUredi

Grelin je otkriven nakon što je receptor za grelin (nazvan receptor za sekretagog hormona rasta tipa 1A ili GHS-R) određen 1999.[2] Naziv hormona zasnovan je na njegovoj ulozi: growth hormone -releasing peptid, s pozivom na korijen protoindoevropska rekonstrukcija/ gʰreh₁-| gʰre– , što znači rasti.[2]

 
Struktura grelina

Gen, transkripcijjski proizvod i strukturaUredi

 
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.[11]

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.[12] Neoktanoilirani oblik je dezacil grelin. Ne aktivira GHS-R receptor, ali ima druge efekte: srčani,[13] antigrelin,[14] appetite stimulation,[15] i inhibicija izlaska glukoze iz jetre.[16] Također su uočeni bočni lanci koji nisu oktanoil: i oni mogu pokrenuti receptor za grelin.[17] Konkretno, utvrđeno je da dekanoil grelin čini značajan dio grelina u opticaju kod miševa, ali od 2011. njegovo prisustvo kod ljudi nije utvrđeno.[18]

Grelinske ćelijeUredi

Alternativni naziviUredi

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).[19]

LokacijaUredi

Grelin ćelije nalaze se uglavnom u želucu [20] i dvanaestpalačnom crijevu, ali također i u jejunumu, plućima i gušteračinim otočićima,[21] gonadama, kori nadbubrežne žlijezde, placenti i bubrezima. Također se pokazalo da se mjestimično luči i u mozgu.[22]

ObilježjaUredi

Grelinske ćelije se nalaze u oksintskim žlijezdama (20% ćelija),[23] piloričnim žlijezdama i tankom crijevu. To su jajolike ćelije sa zrncima (granulama).[24] They have gastrin receptors.[25]Neke proizvode nesfatin-1.[26] Grelinske ćelije se na kraju diferenciraju u gušterači: one su progenitorne ćelije koje tamo mogu stvoriti A-ćelije, PP ćelije i Beta-ćelije.[27]

Funkcija i mehanizam djelovanjaUredi

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 [28]i uzlaznih (aferentnih) i silaznih (eferentnih) vagusnih sigmala.

Grelini i njihve sintetske zamjene (sekretagog hormona rasta povećavaju tjelesnu težinu i masnu masu[29][30][31] ciljajući receptore u the lučnom jezgru[5] koji uključuju neuronski neuropeptid Y (NPY) i agouti-srodni protein (AgRP).[32][6] Ovi neuroni reagirauju na grelin i osetljivi su i na leptin i na insulin.[33] Grelin smanjuje osjetljivost želučanih vagus nih uzlaznih nervnih vlakana, tako da su manje osjetljiva na rastezanje želuca.[34]

Pored svoje funkcije u energetskoj homeostazi, grelin također aktivira holinergijsko-dopaminergijsku nagradnu vezu u ulazima u ventralno tegmentno područje i u mezolimbni put ,[35] krug koji komunicira hedonske i ojačavajuće aspekte prirodnih nagrada,[9] such as food and addictive drugs such as ethanol.[33][36][37] Grelinski receptori nalaze se u neuronima tog kruga.[9][8] Za osjećaj nagrade od alkohola, potrebna je signalizacija hipotalamusnog grelina[38] i ukusna / korisna hrana.[39][40]

Grelin je povezan s izazivanjem apetita i ponašanjem u prehrani. Razina grelina u cirkulaciji je najviša neposredno prije obroka, a najniža neposredno nakon objedovanja.[41][42] Pokazalo se da injekcije grelina kod ljudi i pacova povećavaju unos hrane na način koji ovisi o dozi.[43] Dakle, što se više ubrizga grelina, to se više konzumira. Međutim, grelin ne povećava veličinu obroka, već samo njihov broj.[44] 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.[4]

Razine u krviUredi

Nivoi u krvi su u opsegu pmol/l. Mogu se izmjeriti i aktivni i ukupni grelin.[45] Koncentracije grelina u cirkulaciji rastu prije jela i padaju nakon toga,[41] snažnije kao odgovor na proteine i ugljikohidrate nego na lipide..[18]

Grelinski receptorUredi

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.[46] 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.[12][34]

Mjesto aktivnostiUredi

Metabolizam glukozeUredi

Čitav grelinski sistem (dAG, AG, GHS-R i GOAT) ima gluko-regulatorno djelovanje.[47]

SpavanjeUredi

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.[48]

Reproductivni sistemUredi

Grelin djeluje inhibitorno na sekreciju gonadotropin-oslobađajućeg hormona (GnRH). Može prouzrokovati smanjenu plodnost.[49]

Fetus i novorođenčeUredi

Grelin rano proizvode fetusna pluća i pospješuje njihov rast.[50]Razine grelina u krvi pupčane vrpce pokazuju korelaciju između nivoa grelina i porođajne težine.[45]

Anoreksija i gojaznostUredi

Koncentracija grelina u plazmi gojaznih osoba niža je od one kod mršavijih osoba,[2][51] 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.[52][53]Osobe sa poremećsjrm zvanim anorexia nervosa imaju visok nivo grelina u plazmi[54] u poređenju sa vitkom i normalnom konstitucijom, kao kontrolom.[55][56]Razina grelina raste u doba dana od ponoći do zore kod mršavijih ljudi, što sugerira da postoji mahana u cirkadijskom ritmu gojaznih osoba.[57] Ghrelin levels are high in people with cancer-induced cachexia.[58] Nema dovoljno dokaza da bi se zaključilo bilo za ili protiv upotrebe grelina u liječenju kaheksije povezane s kancerom.[59]

Upravljanje bolestimaUredi

Operacija želučane premosniceUredi

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.[2][60] Studije nisu razjasnile da li se razina grelina vraća u normalu kod ljudi koji su imali operaciju želučane premosnice nakon stabiliziranja gubitka kilograma.[61] Operacija gastričnog bajpasa, koja uključuje gastrektomija vertikalnih rukavaca, dugoročno smanjuje nivo grelina u plazmi za oko 60%.[62]

Također pogledajteUredi

ReferenceUredi

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