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1kits (Ebipipa 10) .
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▎ Enzimba ya Retatrutid
Ensibuko: PubChem |
Omutendera: YA⊃1;QGTFTSDYSI-L⊃2;LDKK4AQA⊃1;AFIEYLLEGGPSSGAPPPS⊃3; Ensengekera ya molekyu: C 221H 342N 46O68 Obuzito bwa molekyu: 4731 g/mol Ennamba ya CAS: 2381089-83-2 PubChem CID: 171390338. Enkola y’okukuuma eddagala lino Ebigambo ebikwatagana:LY3437943 |
▎ Okunoonyereza ku Retatrutid
Retatrutid yakola mu kunoonyereza kuliwa?
Ensibuko y’okunoonyereza eya Retatrutid ekwatagana nnyo n’ensonga z’ensi yonna ezeeyongera okuba ez’amaanyi ez’omugejjo ne ssukaali, awamu n’obuzibu bw’eddagala erijjanjaba eririwo: omugejjo ne sukaali biba bya bulabe nnyo eri obulamu bw’abantu, ng’omuwendo gw’abantu abagejjulukuka mu nsi yonna guteeberezebwa okutuuka ku buwumbi 4.005 mu mwaka gwa 2035 ate omuwendo gw’abalwadde ba ssukaali gweyongera okutuuka ku 592 obukadde, ekivaamu okusaasaanya ssente ennyingi mu by’obulamu mu nsi yonna olw’obulwadde bwa sukaali. Multi-target receptor agonist peptides zivuddeyo nga solution, ezisobola okuziyiza omugejjo, okujjanjaba ssukaali, n’okwewala obutwa obuva mu ddagala eririwo, ekizifuula omuze mu kukola obujjanjabi bw’omugejjo ne sukaali.
Enkola ya Retatrutid ekola ki?
Okulungamya enkyukakyuka y’amasoboza okuyita mu kukola kw’amasoboza amangi
Retatrutid ye agonist ey’okukwata ebitundu bisatu ng’etunuulira ekirungo ekikwata insulinotropic polypeptide ekisinziira ku glucose (GIPR), ekirungo kya glucagon-like peptide-1 receptor (GLP-1R), n’ekirungo kya glucagon receptor (GCGR). Mu kiseera kye kimu kikola ebitundu bino ebisatu ebikwatagana, ne kitereeza enkyukakyuka y’amasoboza okuyita mu makubo agawera.
Ekikolwa kya GIPR agonist:
GIP busimu obufulumya insulini mu byenda obufulumizibwa obutoffaali bwa K obw’ekyenda ne bufulumizibwa oluvannyuma lw’okulya. Retatrutid ekola GIPR, okutumbula okufulumya insulini, okutumbula okuwulira kwa insulini, era bwe kityo n’eyamba omubiri okunyiga obulungi n’okukozesa glucose, bwe kityo ne kikendeeza ku glucose mu musaayi. Okugatta ku ekyo, GIP eyinza okukwata ku nkyukakyuka y’amasavu ng’etereeza enkola y’obutoffaali bw’amasavu n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu [1]..
Enkola ya GLP-1R agonist:
GLP-1 ye hormone ya peptide efulumizibwa obutoffaali bwa L obw’ekyenda. Oluvannyuma lw’okukola GLP-1R, Retatrutid ekola emigaso egy’enjawulo. Kiyinza okusitula okufulumya insulini mu ngeri eyesigamiziddwa ku bungi bwa glucose, bwe kityo ne kikendeeza ku sukaali mu musaayi. Kiyinza okulwawo okufulumya amazzi mu lubuto, okwongera okukkuta n’okukendeeza ku mmere gy’olya. GLP-1R gonism era eyinza okukola ku busimu obw’omu makkati, okutereeza okwagala okulya n’okutebenkeza amaanyi, bwe kityo ne kiyamba mu kugejja [2]..
Ebikolwa bya GCGR agonist:
Glucagon mu bujjuvu ayongera ku mutindo gwa glucose mu musaayi, naye wansi w’okufugibwa Retatrutid, GCGR gonism ekola ebikolwa eby’enjawulo. Kitumbula glycogenolysis ne gluconeogenesis mu kibumba. Wansi w’ebikolwa bya Retatrutid ebigatta, omubiri tegufuna kweyongera kwangu mu miwendo gya glucose mu musaayi wabula mu kifo ky’ekyo gutereeza enkyukakyuka y’amaanyi okwongera okumenya amasavu, bwe kityo ne kituuka ku kugejja n’okulongoosa mu nkyukakyuka y’omubiri. GCGR agonism era eyinza okukosa enkyukakyuka y’amasavu mu kibumba, okukendeeza ku kukuŋŋaanyizibwa kw’amasavu mu kibumba [3]..
Ebikosa Enkola z’omubiri ezikwatagana n’enkyukakyuka y’emmere
Nga ekola mu kiseera kye kimu ku bikwata ebisatu ebyogeddwako waggulu, Retatrutid ekwata ku nkola z’omubiri eziwera ezikwata ku nkyukakyuka y’emmere.
Okulungamya glucose mu musaayi:
Nga ekola GIPR ne GLP-1R okutumbula okufulumya insulini, n’okulungamya obulungi GCGR, Retatrutid esobola okukendeeza ku glucose mu musaayi. Ekikolwa kyayo eky’okukendeeza sukaali kyeyoleka nnyo nga glucose mu musaayi alinnye, so nga tekisuubirwa kuleeta kukendeeza sukaali mu musaayi nga glucose mu musaayi ali wa bulijjo, ekintu eky’omugaso mu kufuga glucose mu musaayi mu balwadde ba ssukaali [4]..
Enzirukanya y’obuzito:
Retatrutid eraga obulungi obw’amaanyi mu kuddukanya obuzito. Nga ekola GLP-1R, ekendeeza ku kufulumya amazzi mu lubuto, eyongera okukkuta, n’okukendeeza ku mmere gy’olya; nga kitereeza enkyukakyuka y’amasavu, kitumbula okumenya amasavu n’okukozesa amaanyi, bwe kityo ne kituuka ku kugejja. Okugezesebwa mu malwaliro kulaga nti abalwadde abagejjulukuka oba abagejjulukuka abajjanjabwa ne Retatrutid bafuna okugejja okw’amaanyi mu kiseera ekigere [5,6]..
Okulungamya amasavu:
Obujjanjabi bwa Retatrutid bulongoosa abalwadde b’amasavu. Kikendeeza ku triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), ne low-density lipoprotein cholesterol (VLDL-C) emiwendo, ate nga era kifuga apolipoproteins, gamba ng’okukendeeza ku apolipoprotein B (apoB) ne apolipoprotein C -III (apoC-III) emiwendo, bwe kityo ne kikendeeza ku muwendo gw’obutundutundu bwa lipoprotein obukwatagana nga balina okuzimba emisuwa n’okutumbula obulamu bw’emisuwa n’emisuwa [7]..
Okulongoosa mu nkyukakyuka y’amasavu mu kibumba:
Ku balwadde abalina obulwadde bw’ekibumba obutali bwa mwenge (NAFLD) obukwatagana n’obutakola bulungi mu nkyukakyuka y’emmere, Retatrutid ekendeeza nnyo amasavu mu kibumba. Mu kugezesebwa okukwatagana, abalwadde abajjanjabwa ne dose ez’enjawulo eza Retatrutid baalaga okukendeera okw’amaanyi mu masavu mu kibumba bw’ogeraageranya n’okusooka, ekiraga nti Retatrutid erina ekikolwa ekirungi eky’okulungamya ku nkyukakyuka y’amasavu mu kibumba, eky’omugaso mu kulongoosa enkola y’ekibumba [3]..
Ekifaananyi 1 Enkola za Retatrutid ez’okukola [8]..
Ebikozesebwa bya Retatrutid bye biruwa?
Obujjanjabi bw’omugejjo:
Omugejjo gufuuse ensonga enkulu ey’ebyobulamu mu nsi yonna, ekwatagana nnyo n’okutandika n’okukulaakulana kw’endwadde ez’enjawulo ezitawona. Retatrutid eraga nti ekola bulungi mu kujjanjaba omugejjo. Abalwadde abagejjulukuka abajjanjabwa n’eddagala lya Retatrutid baafuna okukendeera okw’amaanyi mu buzito bw’omubiri. Mu kunoonyereza okwamala wiiki 48 ku mugejjo ogwa Phase 2, abalwadde abajjanjabiddwa n’eddagala lya Retatrutid erya 8mg ne 12mg baafuna okukendeera kw’obuzito ebitundu 22.8% ne 24.2%. Mu kugezesebwa okulala okwa Phase 2 double-blind, randomized, placebo-controlled trial, abalwadde mu bibinja bya dose ez’enjawulo baafuna diguli ez’enjawulo ez’okugejja ku wiiki 24 ne wiiki 48. Ekibinja kya 12mg kyatuuka ku kugejja ebitundu 24.2% ku wiiki 48, ate ekibinja kya placebo kyalaba okukendeera kwa -2.1% kwokka. Retatrutid ekendeeza bulungi ku buzito bw’omubiri mu balwadde abagejjulukuka, n’ewa ekintu ekipya era eky’amaanyi mu kujjanjaba omugejjo. Obujjanjabi bwa Retatrutid ku mugejjo tebukoma ku kukendeeza ku buzito bwa mubiri wabula buyinza n’okulongoosa ensonga endala ez’ebyobulamu ezikwatagana n’omugejjo, gamba ng’okukendeeza ku situleesi y’okusitula ennyondo n’okumalawo obubonero bw’endwadde z’ennyondo ezeekuusa ku mugejjo nga tuyita mu kugejja; okukendeeza ku buzito nakyo kiyinza okuyamba okulongoosa ebizibu ebiva ku mugejjo nga okusannyalala mu tulo [3,6]..
Obujjanjabi bwa sukaali obw’ekika eky’okubiri:
Ssukaali ow’ekika eky’okubiri bulwadde bwa bulijjo obutawona mu nkyukakyuka y’emmere obumanyiddwa olw’okuziyiza insulini n’obutafulumya insulini emala. Retatrutid erina omugaso oguyinza okukozesebwa mu kujjanjaba ssukaali ow’ekika eky’okubiri. Kisitula okufulumya insulini nga kikola ekirungo kya GLP-1 receptor, kiyamba okuziyiza insulini, n’okukendeeza ku glucose mu musaayi. Ebikolwa byayo eby’okukendeeza ku buzito era biyamba okulongoosa embeera y’abalwadde ba sukaali ow’ekika eky’okubiri, kubanga omugejjo kikulu nnyo mu bulabe eri ssukaali ow’ekika eky’okubiri, era okugejja kuyinza okutumbula okuwulira kwa insulini, okwongera okuyamba mu kufuga glucose mu musaayi. Mu kunoonyereza okwakolebwa ku balwadde ba sukaali ow’ekika eky’okubiri, Retatrutid yaleeta okugejja ennyo n’okukendeera okw’amaanyi mu miwendo gya hemoglobin A1c (HbA1c), nga HbA1c yakendeera ebitundu 1.64% bw’ogeraageranya ne placebo. Kino kiraga nti Retatrutid tekoma ku kufuga bulungi miwendo gya glucose mu musaayi wabula era etereeza embeera okutwalira awamu ey’abalwadde ba sukaali ow’ekika eky’okubiri ng’eyita mu nkola eziwera, omuli okugejja, bwe kityo n’eyongera ku mutindo gw’obulamu bwabwe [6]..
Obujjanjabi bw’obulwadde bw’ekibumba obutaliimu masavu (NAFLD):
NAFLD buvune bw’ekibumba obuva ku situleesi y’enkyukakyuka y’emmere obukwatagana ennyo n’okuziyiza insulini n’okukwatibwa obuzaale, nga buzingiramu embeera ez’enjawulo omuli ekibumba eky’amasavu amangi ekitali kya mwenge, obulwadde bw’ekibumba obutali bwa mwenge, n’obulwadde bwa cirrhosis obukwatagana nabyo. Retatrutid eraga obusobozi obusuubiza mu bujjanjabi bwa NAFLD. Mu kugezesebwa okwa randomized, double-blind, placebo-controlled trial okwazingiramu abeetabye mu kugezesebwa n’obulwadde bw’amasavu mu kibumba obukwatagana n’obutakola bulungi mu nkyukakyuka y’emmere n’amasavu mu kibumba ≥10%, ku wiiki 24, enkyukakyuka eya wakati mu masavu mu kibumba okuva ku ntandikwa yali ya njawulo nnyo mu bibinja bya dose ya Retatrutid: -81.4% mu kibinja kya 8mg, -82.4% mu 12 mg ekibinja, ne +0.3% mu kibinja kya placebo. Kino kiraga nti Retatrutid esobola bulungi okukendeeza ku masavu mu kibumba, ekintu ekikulu ennyo mu kulongoosa endwadde z’ekibumba ez’abalwadde ba NAFLD. Kisuubiza ng’enkola empya ey’obujjanjabi eri NAFLD, eyinza okukendeeza ku kukula kw’obulwadde n’okukendeeza ku bulabe bw’ebizibu eby’amaanyi nga cirrhosis [3]..
Mu bufunzi
Retatrutid eraga obusobozi obusuubiza mu kulongoosa embeera y’obulwadde bw’ekibumba mu balwadde ba NAFLD, ng’ekola okuyita mu nkola eziwera omuli okulungamya enkyukakyuka y’amaanyi, okulongoosa obuziyiza bwa insulini, ebikolwa ebiziyiza okuzimba, n’okukyusakyusa enkyukakyuka y’amasavu.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Rosenstock, J mumanyi wa njawulo era omulimu gwe gukwatagana nnyo n’amatendekero ag’ekitiibwa agawerako, omuli University of Texas Southwestern Medical Center, University of Texas Dallas, ne Canadian VIGOR Centre. Okunoonyereza kwe kukwata ku bintu bingi nga Endocrinology & Metabolism, General & Internal Medicine, Cardiovascular System & Cardiology, Pharmacology & Pharmacy, ne Research & Experimental Medicine. Ebintu ebyewuunyisa bye yakola mu abasomesa bimufudde okusiimibwa ennyo, nga bwe kiragibwa okusunsulwa enfunda eziwera nga 'Highly Cited Researcher in the field of Clinical Medicine' okuva mu 2017 okutuuka mu 2024, ekiraga ekifo kye eky'amaanyi n'obuyinza bwe obw'amaanyi mu kunoonyereza ku by'obujjanjabi. Rosenstock J awandiikiddwa mu kiwandiiko ekijuliziddwa [4].
