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AOD 9604 ni iki?
AOD 9604 ni peptide yubukorikori ikomoka kuri C-terminal (acide amino kumwanya wa 176-191) ya hormone yo gukura kwabantu (HGH), aho fenylalanine kuri N-terminal isimburwa na tirozine. Yabanje gukorwa kugirango ivure umubyibuho ukabije kandi yari igamije kwigana imiterere yo gutwika amavuta ya HGH, ariko idafite ingaruka zo gukura kwimitsi cyangwa izindi ngaruka zijyanye na HGH.
Igikorwa nyamukuru cya AOD 9604 nugukangura lipolysis, gufasha kumena no gusenya ibinure, mugihe bibuza lipogenezi kugirango ibuze amavuta kurya ibiryo bidahinduka mumavuta yumubiri. Ifite akamaro kuruta iyayibanjirije Aod 9401 mugukangura lipolysis nibikorwa byo kurwanya lipogenezi. Byongeye kandi, AOD 9604 irerekana kandi ingaruka nziza kuri diyabete yamagufwa kandi irashobora kugira uruhare mukuvura indwara zamagufwa nka osteoporose.
Akamaro ka AOD 9604 kari mugutanga uburyo bushya bwo kuvura umubyibuho ukabije. Irashobora gufasha abantu gutwika amavuta no guta ibiro neza, mugihe wirinze ingaruka zishobora guterwa na HGH. Byongeye kandi, uburyo bushobora gukoreshwa muri diyabete yamagufa nayo yongerera agaciro ubuvuzi.
Ibyiza bya AOD 9604 harimo ingaruka zayo kuri diyabete yibinure, bitagize ingaruka kumasukari yamaraso cyangwa gukura.
OD AOD 9604 Imiterere
Inkomoko: PubChem |
Urukurikirane: SALLRSIPAPAGASRLLLLTGEIDLP Inzira ya molekulari: C 78H 123N 23O 23S.2 Uburemere bwa molekuline: 1815.1g / mol Numero ya CAS: 221231-10-3 PubChem CID: 71300630 |
▎ AOD 9604 Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na AOD 9604?
AOD 9604 ni peptide igizwe na C-terminal ya hormone yo gukura kwabantu (hGH), cyane cyane aside amine ikurikirana 177 - 191, hamwe n’ibisigisigi bya tirozine kuri N-terminus ya peptide.
Isano iri hagati ya AOD 9604, imisemburo yo gukura, no kuvura umubyibuho ukabije nuburyo bukurikira. Nubwo imisemburo ikura yumuntu (hGH) ifite ubushobozi bwo kuvura umubyibuho ukabije, ibibazo byumutekano bigabanya imikoreshereze yigihe kirekire. Nka C-terminal igice cya hGH, AOD 9604 ifatwa nkigishobora kugira uruhare mukuvura umubyibuho ukabije udateye ingaruka mbi za HGH. Ubushakashatsi bwerekanye ko hGH na AOD 9604 byombi bishobora kugabanya ibiro kandi bikongera lipolytike nyuma yo kuvurwa igihe kirekire mu mbeba. Uburyo bumwe bushoboka ni ugukorana ninzira ya β-adrenergique, cyane cyane na beta (3) -adrenergic reseptors (β3-AR) [1] .
HGH na AOD 9604 zombi zishobora kugabanya uburemere bwumubiri hamwe n’ibinure byumubiri byimbeba zifite umubyibuho ukabije, kandi iki gisubizo kijyanye no kwiyongera kurwego rwa β3-AR RNA, reseptor ya lipolitike nyamukuru muri adipocytes. Icy'ingenzi, byombi HGH na AOD 9604 birashobora kongera urwego β3-AR RNA rwahagaritswe mu mbeba zifite umubyibuho ukabije kugeza ku rwego ugereranije n’izo mu mbeba zinanutse [1] .
Ariko, muri β3-AR imbeba za knockout, gukoresha igihe kirekire hGH na AOD 9604 ntibyashoboye kubyara uburemere kandi byongera lipolysis igaragara mumbeba zo kugenzura ubwoko. Ariko mubushakashatsi bukaze, AOD 9604 irashobora kongera ingufu hamwe na okiside yibinure muri β3-AR imbeba za knockout [1].
Umuti wa osteoarthritis: Gutera inshinge zo mu nda ya AOD 9604 byagaragaje ingaruka zimwe na zimwe zo gukiza muburyo bw'urukwavu rwa osteoarthritis. Ubushakashatsi bwakozwe na Kwon Dong Rak na Park Gi Young bwerekana ko inshinge za ultrasound ziyobowe na intra-articular inshinge za AOD 9604 zongera imbaraga za karitsiye, kandi gutera inshinge AOD 9604 na aside hyaluronike (HA) bifite akamaro kuruta gukoresha HA cyangwa AOD 9604 wenyine [2] .
AOD 9604 yavuzwe ko yigana imiterere ya lipolitike ya hormone yo gukura nta ngaruka mbi yo gutera diyabete. Kubwibyo, irashobora gukoreshwa nkibiyobyabwenge byongera imikorere kandi birabujijwe n’ikigo cy’isi gishinzwe kurwanya ibiyobyabwenge (WADA) [3].
Ubushakashatsi bwibanze kuri AOD 9604 buturuka ahanini ku kwivuguruza hagati yimisemburo ya hormone yo gukura kwabantu mukuvura umubyibuho ukabije nibibazo byumutekano. Muri icyo gihe, hamwe n’ubwiyongere bw’indwara ziterwa na metabolike, uruhare rwayo mu kuzamura ubuzima bwa metabolike n’umutekano wacyo byibanze ku bushakashatsi.
Nibihe biranga nibyiza byuburyo bwibikorwa bya AOD 9604 mugutakaza ibiro no kugenzura metabolike?
Mbere ya byose, kubijyanye na lipolysis, AOD 9604 yongerera cyane sensibilité ya lipolysis ukoresheje β3-adrenergic reseptor (β3-AR) inzira ya adipocytes. Uku gukora gutuma adipocytes igabanya neza triglyceride yabitswe muri aside irike yubusa na glycerol, bityo bigatera kwangirika no gukoresha ibinure kugirango bitange imbaraga kumubiri. Iyi nzira ntabwo ifasha gusa kugabanya ikwirakwizwa ryamavuta yumubiri ahubwo inatezimbere ikwirakwizwa ryamavuta yumubiri, igabanya igipimo cyamavuta yumubiri, bityo bikagabanya ibyago byindwara zitandukanye ziterwa numubyibuho ukabije, nkindwara zifata umutima na diabete yo mu bwoko bwa 2.
Icya kabiri, AOD 9604 nayo ikora neza muguhagarika lipogenez. Irashobora kubuza ibinure ibiryo byinjiye guhinduka ibinure byumubiri muguhindura imiterere ya gen zijyanye na lipogenez. By'umwihariko, AOD 9604 irashobora guhagarika ibikorwa byimisemburo yingenzi ya lipogeneque nka synthase ya fatty acide, bityo bikagabanya synthesis hamwe nububiko bwa aside irike. Izi ngaruka zo kubuza zifasha kugabanya ikwirakwizwa no gutandukanya adipocytes no kwirinda kwaguka gukabije kwimitsi ya adipose, bityo bikagera ku ngaruka zo kugabanya ibiro. Muri icyo gihe, iyi ngaruka yo kubuza irashobora kandi gufasha kugumana uburinganire bwa diyabete yibinure yumubiri no kwirinda indwara ziterwa na metabolike ziterwa no kwegeranya amavuta menshi.
Kubijyanye no guhindura metabolike, uruhare rwa AOD 9604 ruragoye kandi rwuzuye. Irashobora guhindura diyabete yingufu z'umubiri kuva diyabete ya glucose ikajya kuri diyabete yibinure, kandi iri hinduka rifite akamaro kanini mugutakaza ibiro no kuzamura ubuzima bwa metabolike. Mu kongera okiside yangirika ya aside irike, AOD 9604 itanga imbaraga nyinshi mumubiri kandi igabanya guterwa na diyabete ya glucose. Iri tegeko rya metabolike ntirifasha gusa kongera umuvuduko wibanze wa metabolike, bigatuma umubiri ukoresha imbaraga nyinshi kuruhuka, ariko kandi unatezimbere insuline, utera gufata no gukoresha glucose, bityo bikomeza guhagarara neza kurwego rwisukari yamaraso. Byongeye kandi, iyi ngaruka yo kugenzura metabolike ifasha kandi kugabanya ibinure byamavuta mu ngingo nkumwijima, kwirinda no kunoza indwara ziterwa na metabolike nkumwijima wamavuta.
Hanyuma, AOD 9604 ifite ibyiza byihariye mukugabanya insuline. Ugereranije na hormone ikura yuzuye, AOD 9604 ikuraho ingaruka zishobora gutuma insuline irwanya kandi isukari yamaraso ikiyongera. Iri terambere rituma AOD 9604 itekana mugihe cyo kuvura kandi ntabwo bizagira ingaruka mbi kurwego rwisukari yamaraso. Ibi bifite akamaro gakomeye mubuvuzi kubarwayi bafite umubyibuho ukabije, cyane cyane abafite kurwanya insuline cyangwa isukari idasanzwe y'amaraso. AOD 9604 ntishobora kubafasha kugabanya ibiro gusa ahubwo inashobora kunoza insuline, kugabanya ibyago byo kurwara diyabete yo mu bwoko bwa 2, no kuzamura urwego rwubuzima rusange.
Mu gusoza, AOD 9604 igira ingaruka ku kugabanya ibiro no kugenzura metabolike hakoreshejwe uburyo bwinshi bwo gukora, itanga amahitamo mashya n'ibyiringiro byo kuvura umubyibuho ukabije n'indwara ziterwa na metabolike.

Ingaruka za AOD9604 kumubyimba wongera ibiro byimbeba Zucker (fa / fa). Amatungo yipimishije (p) yahawe buri munsi ikinini cyo munwa cya 500 Ìg ya AOD9604 kuburemere bwumubiri muminsi 20, kandi inyamaswa zigenzura (P) zabonye umunyu ungana wa saline burimunsi muburyo bumwe. Ibisubizo ni B B SEM yinyamaswa 8. Itandukaniro rikomeye ryerekanwe hamwe ninyenyeri.
Inkomoko: PubMed [5]
Ni ubuhe buryo bwihariye AOD 9604 ifata diyabete yibinure?
Imikoranire ninzira ya ad-adrenergique: Ubushakashatsi bwerekanye ko hGH nigice cya lipolytike AOD 9604 ikomatanyirijwe muri C-terminal yayo ishobora gutera kugabanuka no kongera lipolytike nyuma yo kuvurwa igihe kirekire mu mbeba [4] . Uburyo bumwe bushoboka ni muburyo bwo guhuza β-adrenergic inzira, cyane cyane na β₃-adrenergic reseptor (β₃-AR). Imbeba zifite umubyibuho ukabije, hGH na AOD 9604 zirashobora kongera urwego rwa imvugo ya β₃-AR RNA kandi zishobora kongera urugero β₃-AR RNA rwahagaritswe ku mbeba zifite umubyibuho ukabije kugeza ku rwego ugereranije n’izo mu mbeba zinanutse. Nyamara, kuvura igihe kirekire β₃-AR imbeba za knockout hamwe na HGH na AOD 9604 zananiwe gutanga impinduka zuburemere kandi byongera lipolysis igaragara mu mbeba zo kugenzura ubwoko. Ariko mubushakashatsi bukaze, AOD 9604 ishobora kongera ingufu hamwe na okiside yibinure muri β₃-AR imbeba za knockout. Ibi byerekana ko ingaruka za lipolitike ya HGH na AOD 9604 zidahuye neza na β₃-AR, nubwo byombi bishobora kongera imvugo ya β₃-AR, bishobora gufasha nyuma yo kongera imbaraga za lipolytike.
Kongera okiside yibinure no gukangura lipolysis: Mu mbeba zifite umubyibuho ukabije (ob / ob) hamwe n’imbeba za C57BL / 6J, ingaruka zidakira z’imisemburo ikura y’umuntu (hGH) na AOD 9604 (C-terminal agace ka HGH) zishobora kugaragara ku buremere bwumubiri, kuringaniza ingufu, no ku gipimo cya okiside. HGH na AOD 9604 byombi byagabanije cyane kwiyongera kwibiro byimbeba zifite umubyibuho ukabije, ibyo bikaba byari bifitanye isano no kwiyongera kwa okiside yibinure mumubiri ndetse no kwiyongera kwa plasma glycerol (ikimenyetso cya lipolysis). Bitandukanye na hGH, AOD 9604 ntabwo itera hyperglycemia cyangwa ngo igabanye insuline. AOD 9604 ntabwo irushanwa na reseptor ya HGH kandi ntabwo itera ikwirakwizwa rya selile nka hGH. Ibi birashimangira kandi igitekerezo cya hGH nka prohormone, byerekana ko igice cya hGH gishobora gukora muburyo butandukanye ninzira gakondo yo gukurura hGH [4] .
Ni izihe ngaruka za AOD 9604 ku mwijima?
Ingaruka ya AOD 9604 ku mwijima igaragarira cyane cyane ku ngaruka zayo kuri diyabete y’ibinure. Nka polypeptide ya sintetike yigana imiterere ya lipolitike ikora ya hormone yo gukura kwabantu (hGH), AOD 9604 irashobora guteza imbere lipolysis, ikabuza lipogenezi, kandi igahindura diyabete yingufu z'umubiri kuva diyabete ya glucose ikajya kuri diyabete yibinure. Ubu buryo bwibikorwa bufasha kugabanya ikwirakwizwa ryamavuta mu mwijima, bityo bigatanga urugero runaka rwo kurinda umwijima. Ku ndwara ziterwa na metabolike nk'umwijima w'amavuta, kugabanya ibiro n'ingaruka zo kugenzura metabolike ya AOD 9604 birashobora gufasha kuzamura imiterere ya diyabete yibinure y'umwijima, kugabanya umutwaro ku mwijima, bityo bigatuma imikorere y'umwijima inoze. Ariko, kuri ubu hariho ubushakashatsi buke butaziguye ku ngaruka za AOD 9604 ku mwijima. Ingaruka zavuzwe haruguru ziteganijwe ahanini zishingiye ku ngaruka zagize kuri diyabete y’ibinure, kandi haracyakenewe ubushakashatsi bwa siyansi kugira ngo hamenyekane ingaruka zihariye zo kurinda umwijima n’uburyo bukoreshwa.
AOD 9604 isobanura iki?
AOD 9604 ni polypeptide ya sintetike yigana imiterere ya lipolytike ikora ya hormone yo gukura kwabantu (HGH), kandi agaciro kayo mubuvuzi ni ngombwa. Mu kuvura umubyibuho ukabije n'indwara ziterwa na metabolike, AOD 9604 irashobora guteza imbere neza lipolysis, ikabuza lipogenezi, kandi ikagenga imikorere ya metabolike y'umubiri, ifasha abarwayi bafite umubyibuho ukabije guta ibiro, kunoza imiterere y'umubiri, kandi ifite agaciro gakoreshwa mu kuvura indwara ziterwa na metabolike nk'umwijima w'amavuta. Ugereranije na hormone yuzuye yo gukura, ikuraho ingaruka zishobora gutera insuline no kurwanya isukari mu maraso, bityo bikaba bifite umutekano mugihe cyo kuvura kandi bikwiriye abarwayi benshi.
AOD 9604 ifite akamaro gakomeye mubushakashatsi bwubushakashatsi niterambere. Nkumuti ugabanya ibiro hamwe nuburyo bwihariye bwibikorwa, utanga amahitamo mashya yo kuvura umubyibuho ukabije, ukerekana ubushobozi bwimiti ya polypeptide mukuvura indwara ziterwa na metabolike, ikanatanga ibitekerezo bishya hamwe nubuyobozi bwubushakashatsi kugirango habeho iterambere ryimiti yizewe kandi yizewe. Byongeye kandi, synthesis hamwe nubushakashatsi bwa AOD 9604 byateje imbere iterambere ryurwego rwibiyobyabwenge bya polypeptide, bigenzura niba bishoboka ko imiti ya polypeptide yigana no kugenzura imikorere yihariye yumubiri mu mubiri, ikanatanga uburambe bwagaciro mugushushanya, guhuza, no kunoza imiti ya polypeptide.
Mugutezimbere ubuzima buzira umuze, AOD 9604 irashobora gukoreshwa nkuburyo bwabafasha gufasha abantu kugenzura ibiro byabo no gukomeza ubuzima bwiza. Umubyibuho ukabije ni ikibazo gikomeye muri societe igezweho, kandi ingaruka zacyo zo kugabanya ibiro zirashobora gutanga infashanyo yinyongera kubantu bafite ikibazo cyo guta ibiro binyuze mumirire yoroshye no gukora siporo. Muri icyo gihe, mu kugenzura diyabete y’ibinure, ifasha kuzamura ubuzima bw’umubiri mu mibereho, kugabanya urugero rwa lipide mu maraso, kugabanya ibinure mu mitsi y’amaraso, kugabanya ibyago by’indwara ziterwa na metabolike nk’indwara zifata umutima, ndetse no kuzamura imibereho.
AOD 9604 nayo igira uruhare runini mugutezimbere ubushakashatsi bwibanze. Ubushakashatsi bwabwo bufasha gucukumbura cyane imikorere yimikorere ya hormone yo gukura kwabantu, cyane cyane uruhare rwayo ninzira yerekana inzira mugutunganya diyabete yibinure. Binyuze mu bushakashatsi bwakozwe kuri AOD 9604, abahanga barashobora kumva neza uburyo imisemburo ikura ikora imirimo yayo ya physiologique binyuze mumikoranire hagati ya domaine yihariye niyakira, nuburyo iyi mikorere ihinduka mubihe bitandukanye bya physiologique na patologi. Byongeye kandi, AOD 9604 irashobora gukoreshwa nkigikoresho cyubushakashatsi mubushakashatsi bujyanye na diyabete y’ibinure, bifasha abahanga kwiga inzira yo kubora ibinure, ibisekuruza, hamwe no kwanduza ibimenyetso bya selile, kwerekana uburyo bwa molekile hamwe n’imiyoboro igenga diyabete y’ibinure, no gutanga ishingiro ry’imyumvire yo guteza imbere uburyo bwo kuvura n’ibiyobyabwenge bya diyabete idasanzwe.
Umwanditsi w'ikinyamakuru
Heffernan, MA yifatanije na kaminuza ya Limerick kandi akora mubyiciro byinshi byamasomo. Harimo Endocrinology & diabete, aho ubushakashatsi bushobora kwibanda kumikorere ya hormone hamwe na metabolike mumubiri. Muri siyanse ya Polymer, akazi kabo gashobora kuba karimo kwiga ibikoresho bya polymer, synthesis, imitungo, nibisabwa. Physiology yakubiyemo imikorere nibikorwa byibinyabuzima, mugihe imirire & Dietetics bijyanye na siyanse yibiribwa, imirire, hamwe nimirire.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Ubushakashatsi bwa Heffernan bushobora gukora ubushakashatsi ku masangano y’izi nzego, nko guteza imbere sisitemu yo gutanga imiti ishingiye kuri polymer y’indwara ziterwa na metabolike cyangwa kwiga ingaruka ziterwa na physiologique ziterwa n’imirire hakoreshejwe tekinoroji ya siyansi yateye imbere. Ibikorwa byabo bigira uruhare mu gusobanukirwa byimazeyo inzira y'ibinyabuzima no guteza imbere ibisubizo bishya mubuvuzi na siyanse y'ibikoresho. Heffernan, MA yashyizwe ku rutonde rwerekana [4].
Imirongo ijyanye
[1] Heffernan M, Impeshyi RJ, Thorburn A, nabandi. Ingaruka za GH zabantu hamwe nigice cya lipolytike (AOD9604) kuri diyabete ya lipide nyuma yo kuvurwa karande ku mbeba zifite umubyibuho ukabije nimbeba β3-AR zikubita [J]. Endocrinology, 2001,142 (12): 5182-5189.DOI: 10.1210 / en.142.12.5182.
[2] Kwon DR, Parike G Y. Ingaruka zo Gutera Imbere-articular Gutera AOD9604 hamwe na Acide ya Hyaluronic cyangwa idafite muri Moderi y'urukwavu Osteoarthritis [J]. Umwaka w'ubumenyi bwa Clinical na Laboratoire, 2015,45 (4): 426-432. http://www.annclinlabsci.org/content/45/4/426.ururimi
[3] Cox HD, Smeal SJ, Hughes CM, n'abandi. Kumenya no muri diyabete ya vitro ya AOD9604 [J]. Kwipimisha no gusesengura ibiyobyabwenge, 2015,7 (1): 31-38.DOI: 10.1002 / dta.1715.
[4] Heffernan MA, Thorburn AW, Fam B, n'abandi. Kwiyongera kwa okiside yibinure no kugabanya ibiro ku mbeba zifite umubyibuho ukabije ziterwa no kuvura karande hamwe na hormone yo gukura kwabantu cyangwa igice cyahinduwe C-terminal [J]. Ikinyamakuru mpuzamahanga cy’umubyibuho ukabije, 2001,25 (10): 1442-1449.DOI: 10.1038 / sj.ijo.0801740.
[5] Ng FM, Sun J, Sharma L, n'abandi. Ubushakashatsi bwa Metabolic ya Lipolytike ya Sintetike (AOD9604) ya Hormone yo Gukura kwabantu [J]. Ubushakashatsi bwa Hormone mubuvuzi bw'abana, 2001,53: 274-278. DOI: 10.1159 / 000053183
INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.