Cocer Peptides ye ŋlɔe 
ŋkeke 25 enye sia
NYATAKAKAWO KPLE NUSIWO WOTSƆ ƑE NYATAKAKA SIWO KAtã WOÐO LE NYATAKAKADZRAÐOƑE SIA ME LA KPLE NYATAKAKAWO kaka KPLEE NUFIAFIA ƑE TAÐOÐOWO KO.
Wotrɔ asi le atike siwo wona le nyatakakadzraɖoƒe sia ŋu na numekuku le vitro ɖeɖeko. Wowɔa numekuku le vitro (Latingbe me: *le ahuhɔ̃e me*, si gɔmee nye le ahuhɔ̃e me) le amegbetɔ ƒe ŋutilã godo. Atike siawo menye atikewo o, United States ƒe Nuɖuɖu Kple Atike Ŋuti Dɔwɔƒe (FDA) meda asi ɖe wo dzi o, eye mele be woazã wo atsɔ axe mɔ ɖe atikewɔwɔ, dɔléle, alo dɔléle aɖeke nu, adae, alo adae o. Se de se vevie be woatsɔ atike siawo ade amegbetɔ alo lãwo ƒe ŋutilã me le mɔ ɖesiaɖe nu.
AOD9604 ƒe gɔmesese
AOD9604 nye peptide si woɖe tso amegbetɔ ƒe tsitsi ƒe lãmetsi (hGH) ƒe C-nuwuƒe kakɛ me. Amino acid 177–191 siwo nye hGH ye le eme, eye wotsɔ tyrosine ƒe akpa bubu (Tyr) kpe ɖe eŋu le peptide la ƒe N-nuwuƒe, si nye Tyr-hGH 177–191. AOD9604 ƒe amino acid ƒe ɖoɖoe ɖoa eƒe teƒe ƒe nɔnɔme, si hã kpɔa ŋusẽ ɖe eƒe kadodo kple xɔla kple molecule vovovo siwo le ŋutilãa me dzi. Tyrosine ƒe akpa si susɔ si wotsɔ kpe ɖe N-nuwuƒea ate ŋu akpɔ ŋusẽ ɖe peptide la ƒe liƒo le ŋutilã me, lãmenugbagbeviwo ƒe xɔxlɔ̃ nyuie, kple kadodo ƒe ƒomedodo kple xɔla tɔxɛwo dzi. AOD9604 le peptide ƒe ƒuƒoƒo me, siwo kpɔa gome le ŋutilã ƒe dɔwɔwɔ vovovowo me le ŋutilã me, abe dzesiwo ƒe tɔtrɔ kple lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe ɖoɖowɔwɔ ene. Le eƒe dzɔtsoƒe kple eƒe wɔwɔme tɔxɛ ta la, ŋutilã ƒe dɔwɔwɔ tɔxɛwo le AOD9604 si, vevietɔ eɖea ŋusẽkpɔɖeamedzi veviwo fiana le ami ƒe asitɔtrɔ le lãme na ame ƒe ɖoɖowɔwɔ me.
Mɔnu si AOD9604 wɔna le Lipid Metabolism Dzikpɔkpɔ me
(1) Hadede kple β-adrenergic mɔa
β-adrenergic receptor ƒe ɖeɖefia dzi kpɔkpɔ: AOD9604 ate ŋu akpɔ ŋusẽ ɖe lipid ƒe asitɔtrɔ dzi to nuwɔwɔ kple β-adrenergic mɔ dzi, vevietɔ to β(3)-adrenergic receptor (β(3)-AR) ƒe ɖoɖowɔwɔ me. Le sisiblisi lolo akpa ƒe kpɔɖeŋu me la, le AOD9604 dodo ɖe dɔgboa me ŋkeke 14 tsiã ɖe enu megbe la, β(3)-AR RNA ƒe ɖeɖefia ƒe agbɔsɔsɔ le ami me dzi ɖe edzi. β(3)-AR ye nye lipolytic receptor vevitɔ le adipocytes me, eye eƒe ɖeɖefia si dzi ɖe edzi doa lipolysis ɖe ŋgɔ. AOD9604 ate ŋu ana β(3)-AR domenyiŋusẽfianu ƒe ɖeɖefia nanyo ɖe edzi to dzesimɔ siwo do ƒome kplii ƒe dɔwɔwɔ me, si ana eƒe gotagome ɖeɖefia nadzi ɖe edzi le lãmenugbagbeviwo me. Ate ŋu akpɔ ŋusẽ ɖe nuŋɔŋlɔ ƒe akpa aɖewo ƒe kadodo kple β(3)-AR domenyiŋusẽfianu ƒe promoter nuto dzi, si ana domenyiŋusẽfianu ƒe nuŋɔŋlɔ gɔmedzedze nawɔ dɔ nyuie wu.
The cascading reactions of β-adrenergic pathway activation: Ne β(3)-AR ƒe ɖeɖefia dzi ɖe edzi la, eblana ɖe ligandwo ŋu be wòana dzesimɔ siwo le anyime la nawɔ dɔ. β(3)-AR si wowɔ dɔ la wɔa ɖeka kple G proteinwo, si wɔnɛ be adenylate cyclase wɔa dɔ, si hã dzia dɔla evelia ƒe cyclic adenosine monophosphate (cAMP) ƒe agbɔsɔsɔ ɖe lãmenugbagbeviwo me ɖe edzi. cAMP naa protein kinase A (PKA) wɔa dɔ, si naa phosphorylate kple hormone-sensitive lipase (HSL), si nye enzyme vevi aɖe le lipolysis me si naa triglycerides ƒe tsi me ʋuʋu va zua fatty acids kple glycerol, si wɔnɛ be lipolysis doa ŋgɔ eye wònaa lipid metabolism nɔa ɖoɖo nu.
(2) Nusiwo dona tso eme tẽ le wo ɖokui si le β(3)-AR me
Nusiwo wokpɔ le dodokpɔ me kpata: Le dodokpɔ sesẽ siwo wowɔ le β(3)-AR domenyiŋusẽfianu-knockout mice ŋu me la, AOD9604 gadzi ŋusẽzazã kple ami ƒe oxidation ɖe edzi kokoko. Esia fia be AOD9604 ƒe ɖoɖowɔwɔ ƒe ŋusẽkpɔɖeamedzi ɖe lipid ƒe asitɔtrɔ dzi menɔ te ɖe β(3)-AR dzi bliboe o. Togbɔ be womese mɔnu tɔxɛa gɔme bliboe haɖe o hã la, mɔ bubuwo alo afɔɖeɖe tẽ ƒe taɖodzinuwo ate ŋu anɔ anyi. AOD9604 ate ŋu awɔ dɔ ɖe mitochondria dzi tẽ, akpɔ ŋusẽ ɖe mitochondria ƒe dɔwɔwɔ dzi eye wòana ami ƒe β-oxidation nadzi ɖe edzi. Mitochondria nye lãmenugbagbeviwo ƒe ŋusẽ ƒe asitɔtrɔ ƒe teƒe veviwo, eye ami ƒe β-oxidation dzɔna le mitochondria me. AOD9604 ateŋu ado ami ƒe gege ɖe mitochondria me ɖe ŋgɔ eye wòana oxidative ƒe gbegblẽ nanɔ bɔbɔe to ʋuɖoɖo proteinwo alo enzyme siwo do ƒome kplii ƒe dɔwɔwɔ dzi kpɔkpɔ le mitochondria ƒe lãkusi dzi, si ana ŋusẽzazã kple ami ƒe oxidation nadzi ɖe edzi.
Dzesimɔ bubu siwo ate ŋu ana: AOD9604 hã kpɔa gome le dzesimɔ bubuwo dzi kpɔkpɔ me. Ate ŋu akpɔ ŋusẽ ɖe peroxisome proliferator-activated receptor (PPAR) ƒomea ƒe dɔwɔwɔ dzi. PPAR-wo nye nuklia-xɔla ƒe hatsotso aɖe si wɔa akpa vevi aɖe le ɖoɖowɔwɔ me le ami ƒe asitɔtrɔ, ŋusẽ ƒe dadasɔ, kple dɔdzẽ ƒe ŋuɖoɖowo me. AOD9604 ate ŋu awɔ nu kple PPARwo atsɔ aɖɔ woƒe domenyiŋusẽfianu siwo woɖo taɖodzinu na ƒe ɖeɖefia ɖo, si ana wòakpɔ ŋusẽ ɖe domenyiŋusẽfianu siwo do ƒome kple ami ƒe asitɔtrɔ ƒe nuŋɔŋlɔ kple wo gɔmeɖeɖe dzi, si ana wòaɖɔ lipid ƒe asitɔtrɔ ɖo. Ate ŋu akpɔ gome le insulin ƒe dzesimɔa ƒe ɖoɖowɔwɔ hã me. Togbɔ be suklidɔ ƒe nugbegblẽ le ame ŋu si do ƒome kple hGH mele AOD9604 ŋu o hã la, ate ŋu akpɔ ŋusẽ ɖe ʋumemi ƒe asitɔtrɔ ƒe dɔwɔwɔ dzi le mɔ si mele tẽ o nu to insulin ƒe dzesimɔa ɖɔɖɔɖo nyuie me.
AOD9604 ƒe ŋusẽkpɔɖeamedziwo
(1) Ŋusẽkpɔɖeamedzi ɖe Ŋutilã ƒe Kpekpeme Kple Ami Dzi
Lãwo ƒe dodokpɔ ƒe kpeɖodzi: Le sisiblisi lolo akpa ƒe kpɔɖeŋu me la, AOD9604 dodo ɖe dɔgboa me ɣeyiɣi didi (ŋkeke 14 ƒe dodo atraɖii) ɖe ŋutilã ƒe kpekpeme kple ami si le ŋutilã me dzi kpɔtɔ ŋutɔ. Wotsɔ ŋutilã ƒe kpekpeme kple ami ƒe ɖiɖi sia do ƒome kple β(3)-AR RNA ƒe ɖeɖefia ƒe agbɔsɔsɔ si dzi ɖe edzi, si ɖee fia be AOD9604 doa lipolysis ɖe ŋgɔ to β(3)-AR ƒe ɖeɖefia dzi kpɔkpɔ me, si wɔnɛ be ŋutilã ƒe kpekpeme kple ŋutilã me ami dzi ɖena kpɔtɔna. Etɔxɛe la, ami si le ŋutigbalẽ te kple esi le lãkusi me ƒe kpekpeme dzi ɖe kpɔtɔ, tsɔ kpe ɖe lolo bliboa dzi ɖeɖe kpɔtɔ ŋu. Le dodokpɔa me la, sisiblisi ƒe kpekpeme dzidzedze edziedzi kple ami ƒe lãkusi ƒe kpekpeme dzidzedze pɛpɛpɛ le amekuku megbe ɖee fia be sisiblisi siwo wotsɔ AOD9604 da dɔe ƒe kpekpeme kple ami ƒe kpekpeme dzi ɖe kpɔtɔ ŋutɔ ne wotsɔe sɔ kple ƒuƒoƒo si me wokpɔa wo gbɔ le, eye edziɖeɖe sia ɖe nɔnɔme si nɔ te ɖe agbɔsɔsɔme si wozã dzi fia.
Figure 2 Atikewo ƒe Taɖodzinuwo Fifia Kple Etsɔme le Kpekpeme Dzikpɔkpɔ Me
Le amegbetɔ ƒe lolo akpa dada gome la, AOD9604 ƒe ŋusẽkpɔɖeamedziwo lé asixɔxɔ si ate ŋu azãe ɖe asi. Lolo akpa nye afɔku vevi aɖe na dɔléle geɖe siwo nɔa anyi didi abe dzitodzito me dɔléle kple suklidɔ ene, eye ame ƒe kpekpeme kple ami dzi ɖeɖe kpɔtɔ le vevie ŋutɔ be wòana dɔnɔ siwo lolo akpa ƒe lãmesẽ nanyo ɖe edzi.
(2) Ŋusẽkpɔɖeamedzi ɖe Ŋusẽ ƒe Trɔtrɔ Ŋu
Ŋusẽzazã ƒe Dzidziɖedzi: AOD9604 dzia ŋusẽzazã ɖe edzi le mice siwo sɔ kple β(3)-AR domenyiŋusẽfianu knockout mice siaa me. Le mi siwo sɔ me la, wozã calorimetry si metso tẽ o tsɔ dzidze oxygen zazã kple carbon dioxide ƒe wɔwɔ, si ɖee fia be AOD9604 dzi ŋusẽ ƒe asitɔtrɔ ƒe agbɔsɔsɔ ɖe edzi ŋutɔ. Wogblɔ be ŋusẽkpɔɖeamedzi sia tso AOD9604 si doa lipolysis ɖe ŋgɔ gbɔ, eye ami siwo dona le eme la nyea ŋusẽ ƒe gɔmeɖoanyiwo na oxidation kple wo zazã, si wɔnɛ be ŋusẽzazã dzina ɖe edzi. Le β(3)-AR knockout mice me la, togbɔ be eƒe dɔwɔwɔ ƒe mɔnu menɔ te ɖe β(3)-AR dzi o hã la, wogakpɔ ŋusẽzazã ƒe dzidziɖedzi kokoko, si gaɖee fia be ŋusẽ ƒe asitɔtrɔ ƒe ɖoɖowɔwɔ ƒe mɔnu aɖe le AOD9604 si si le eɖokui si tso β(3)-AR gbɔ.
Ami ƒe oxidation ƒe ɖoɖowɔwɔ: AOD9604 doa ami ƒe oxidation ƒe ɖoɖoa ɖe ŋgɔ. Le lãmenugbagbeviwo ƒe dodokpɔwo me la, wozã ami siwo wotsɔ keklẽŋusẽ de dzesii tsɔ lé ŋku ɖe woƒe oxidative metabolism ŋu la, wokpɔe be ami ƒe oxidation ƒe agbɔsɔsɔme dzi ɖe edzi le lãmenugbagbevi siwo wotsɔ AOD9604 da dɔe me. Menye ɖeko esia kpena ɖe ame ŋu be ami ƒe dzadzraɖo dzi naɖe akpɔtɔ ko o, ke enaa ŋusẽ geɖe wu hã ŋutilãa. AOD9604 ate ŋu ana ami ƒe oxidation ƒe dɔwɔwɔ nanyo ɖe edzi to mitochondrial ƒe dɔwɔwɔ dzi kpɔkpɔ me, si ana mitochondrial biogenesis kple dɔwɔwɔ nadzi ɖe edzi. Edoa enzyme siwo do ƒome kple ami ƒe oxidation le mitochondria me ƒe ɖeɖefia kple dɔwɔwɔ ɖe ŋgɔ, siwo dometɔ aɖewoe nye carnitine palmitoyltransferase I (CPT-I), si nye enzyme vevitɔ si ɖoa seɖoƒe na ami siwo gena ɖe mitochondria me hena oxidation. AOD9604 ate ŋu ado ami ƒe gege ɖe mitochondria me ɖe ŋgɔ hena oxidative decomposition to CPT-I ƒe ɖeɖefia dzi ɖeɖe kpɔtɔ me.
(3) Ŋusẽ si wòkpɔna ɖe aklã me ʋumemi ƒe asitɔtrɔ dzi
Hepatic lipid metabolism animal experiment study: Le sisiblisi ƒe aklã si me ami le ƒe kpɔɖeŋu aɖe me la, wowɔ numekuku le ŋusẽ si AOD9604 kpɔna ɖe aklã me lipid metabolism dzi ŋu. Woma sisiblisiwo ɖe ƒuƒoƒo si me wokpɔa wo gbɔ le, kamedede ƒe ƒuƒoƒo, kamedede + AOD9604 ƒuƒoƒo, kple AOD9604 ɖeɖeko ƒe atikewɔwɔ ƒe ƒuƒoƒo me. Nusiwo do tso eme ɖee fia be alanine aminotransferase (ALT) ƒe agbɔsɔsɔ le AOD9604 ɖeɖeko ƒe ƒuƒoƒoa kple kamedede + AOD9604 ƒuƒoƒoa me ɖiɖi ŋutɔ wu esiwo le ƒuƒoƒo si me wokpɔa wo gbɔ le, si ɖee fia be AOD9604 kpɔa ŋusẽ aɖe ɖe aklã ƒe gbegblẽ dzi. Woate ŋu agblɔ be esia tso AOD9604 si kpɔa ami ƒe asitɔtrɔ le aklã me dzi, si ɖea ami ƒe ƒoƒo ɖe aklã me dzi kpɔtɔna, si wɔnɛ be aklã ƒe ʋuʋudedi kple dɔdzẽ ƒe ŋuɖoɖowo dzi ɖena kpɔtɔna.
Ŋusẽkpɔɖeamedzi ɖe aklã me enzymewo kple cytokeratin-18 (CK18) dzi: Cytokeratin-18 nye biomarker si ɖea aklã me lãmenugbagbeviwo ƒe tsɔtsrɔ̃ fiana. Le dodokpɔa me la, togbɔ be AOD9604 ƒe atike ɖeka zazã ƒe ƒuƒoƒoa meɖe CK18 ƒe agbɔsɔsɔ dzi kpɔtɔ boo o hã la, mehe ŋusẽkpɔɖeamedzi gbegblẽwo hã vɛ o. Esia fia be AOD9604 ate ŋu akpɔ ŋusẽ ɖe aklã me lãmenugbagbeviwo ƒe apoptosis ƒe ɖoɖoa dzi le mɔ si mele tẽ o nu to aklã me ʋumemi ƒe asitɔtrɔ dzi, si ana wòakpɔ aklã me lãmenugbagbeviwo ta tso nusiwo agblẽ le wo ŋu me vaseɖe afi aɖe. AOD9604 ate ŋu alé aklã me ʋumemi ƒe asitɔtrɔ ƒe dadasɔ me ɖe asi to domenyiŋusẽfianu siwo do ƒome kple ami ƒe wɔwɔme, etsɔtsɔ yi teƒe bubu, kple eƒe gbegblẽ le aklã me ƒe ɖeɖefia dzi kpɔkpɔ me, si ana ami ƒe ƒoƒo ɖe aklã me si mesɔ o dzi naɖe akpɔtɔ.
AOD9604 ƒe dɔwɔwɔwo
(1) Nusiwo Woate Ŋu Azã Le Lolo akpa Dada Me
Viɖewo Kple Mɔkpɔkpɔwo: Ne wotsɔ AOD9604 sɔ kple atike xoxo siwo wozãna tsɔ ɖea lolo dzi kpɔtɔna la, viɖe geɖe ate ŋu anɔ AOD9604 ŋu. Suklidɔ ƒe nugbegblẽ le ame ŋu si do ƒome kple hGH mele eme o. hGH ate ŋu ahe nu gbegblẽwo abe insulin ƒe dɔlélenutsiŋutete kple sukli ƒe agbɔsɔsɔ si dzina ɖe ʋu me vɛ ne wozãe tsɔ da lolo akpa. AOD9604 ƒoa asa na nugbegblẽ siawo to eƒe xɔtuɖoɖo tɔxɛa dzi. AOD9604 ate ŋu aɖɔ ami ƒe asitɔtrɔ ɖo koŋ, ado ami ƒe gbagbã ɖe ŋgɔ, eye wòana ŋusẽzazã nadzi ɖe edzi, si ana atikewɔwɔ ƒe mɔkpɔkpɔ nyuiwo nasu dɔnɔ siwo lolo akpa bɔbɔe la si. Eƒe dɔwɔwɔ ƒe mɔnu lɔ agbɔsɔsɔ vovovowo ɖe eme, menye to β-adrenergic mɔa dzi kpɔkpɔ me ko o, ke to mɔnu si mewɔ ɖeka kple β(3)-AR o hã dzi, si naa nudede nyawo me ƒe mɔnu si de to wu le lolo akpa dada me.
(2) Nusiwo woate ŋu azã le aklãdɔlélewo dada me
Alesi woate ŋu ada aklãdɔ si me ami mele o (NAFLD): NAFLD nye aklãdɔ si bɔ si ƒe dzesi enye ami si ƒoa ƒu ɖe aklã me fũu akpa. Le aklãdɔ si me ami le ƒe kpɔɖeŋu si wowɔ le sisiblisi me la, AOD9604 ate ŋu aɖɔ aklã me ʋumemi ƒe asitɔtrɔ ɖo, aɖe ami si le aklã me dzi akpɔtɔ, eye wòana aklã ƒe dɔwɔwɔ ƒe dzesiwo nanyo ɖe edzi. Asixɔxɔ aɖe le AOD9604 ŋu le dɔwɔwɔ me na NAFLD dada. Ate ŋu aɖe ami ƒe ƒoƒo ɖe aklã me dzi akpɔtɔ to ami ƒe gbagbã kple eƒe tsɔtsɔ yi aklã me dodo ɖe ŋgɔ me, si ana aklã ƒe ʋuʋudedi kple dɔdzẽ ƒe ŋuɖoɖowo dzi naɖe akpɔtɔ. AOD9604 ate ŋu aɖɔ oxidative stress kple inflammatory signaling pathways le aklãa me hã ɖo, si agakpɔ aklã me lãmenugbagbeviwo ta tso nusiwo agblẽ le wo ŋu me.
Nyanuwuwuw
Abe peptide si wokpɔ tso amegbetɔ ƒe tsitsi ƒe lãmetsi ƒe C-nuwuƒe nuto me ene la, AOD9604 ƒe dɔwɔwɔ ƒe mɔnu le ʋumemi ƒe asitɔtrɔ dzi kpɔkpɔ me lɔ kadodo kple β-adrenergic mɔa kple ŋusẽkpɔɖeamedzi tẽ siwo mewɔ ɖeka kple β(3)-AR o ɖe eme. To mɔnu siawo dzi la, AOD9604 ɖea ŋutilã ƒe kpekpeme kple ŋutilã me ami dzi kpɔtɔna nyuie, edzia ŋusẽzazã ɖe edzi, enaa ami ƒe oxidation nɔa ɖoɖo nu, eye wònaa aklã me ʋumemi ƒe asitɔtrɔ nyona ɖe edzi. Le eŋudɔwɔwɔ gome la, ŋugbedodo gã aɖe le AOD9604 ŋu le lolo akpa, kamedefefe ƒe atikewɔwɔ, kple aklãdɔ dada me.
Dzɔtsoƒewo
[1] Dehbashi M, Fathi M, Attarzadeh Hosseini S. R., kple ame bubuwo. Ŋusẽ si Kwasiɖa Enyi ƒe Dzidodo ƒe Hehenasuku, Somatropin Dodo, Kple Eƒe Lipolytic Fragment (AOD9604) kpɔ ɖe Cytokeratin-18 kple aklã me dɔlékuiwo dzi le Mice si na aklã ƒe gbegblẽ le nuɖuɖu si me ami sɔ gbɔ ɖo ta[J]. Ɣleti etɔ̃ ƒe agbalẽ si nye Atikewɔwɔ Ŋuti Nunya ƒe Dzogoe, 2021,27:502-517.DOI:10.32598/hms.27.4.3513.1.
[2] Cox H. D., Smeal S. J., Hughes C. M., kple ame bubuwo. AOD9604[J] ƒe lãmenugbagbeviwo ƒe dzedze kple eƒe lãmenugbagbeviwo ƒe dɔwɔwɔ le vitro. Atikewo Dodokpɔ Kple Wo Me Dzodzro, 2015, 7 (1): 31-38.DOI: 10.1002 / dta.1715.
[3] Stier H, Vos E, Kenley D L. Dedienɔnɔ kple Mɔɖeɖe ɖe Hexadecapeptide AOD9604 ŋu le Amegbetɔwo me[J]. Journal of Endocrinology kple lãmenugbagbeviwo ƒe dɔwɔwɔ, 2013,3:7-15.
https://api.semanticscholar.org/CorpusID: 56559133. Ƒe 1999 ƒe ɣleti gbãtɔ me
[4] Witkamp R F. Fifia kple Etsɔme Atikewo ƒe Taɖodzinuwo le Kpekpeme Dzikpɔkpɔ me[J]. Atikewɔwɔ Ŋuti Numekuku, 2011, 28 (8): 1792-1818.DOI: 10.1007 / s11095-010-0341-1.
Adzɔnu si li na numekuku zazã ɖeɖeko:
