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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?
Omugejjo kye kimu ku bizibu ebikulu eby’obulamu bw’abantu ennaku zino. Omugejjo guyinza okuvaako ebizibu by’obulamu eby’enjawulo, gamba ng’okukyusakyusa emmere ey’ekika eky’okubiri, endwadde z’emisuwa, puleesa, okukendeera kw’amasavu mu musaayi, n’obulwadde bw’ekibumba obw’amasavu obutali bwa mwenge. Olw’okweyongera kw’abagejjo obutasalako, waliwo obwetaavu obweyongera obw’obujjanjabi obupya obusobola okuddukanya obulungi obuzito bw’omubiri n’okutumbula embeera y’obulamu [1] . Wadde ng’okukyusakyusa mu bulamu, gamba ng’okwongera okukola emirimu gy’omubiri n’okukendeeza ku mmere gye balya, ze nkola enkulu ez’okugejja, okukuuma omugejjo okumala ebbanga eddene kikyali kusoomoozebwa eri abantu abakulu bangi abakoseddwa. Retatrutid ye agonist ey’ekipya ey’okukwata ebitundu bisatu ekola ku kirungo kya glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), ne glucagon receptor (GCGR). Enkola eno ey’okukola eya multi-receptor egiwa enkizo ez’enjawulo mu kugejja. Bw’ogeraageranya n’eddagala erikendeeza ku buzito erikola ku kifo ekimu ekikwata, Retatrutid esobola okulung’amya mu bujjuvu enkola z’omubiri ez’okukyusakyusa ebiriisa [1] . Retatrutid etuuka ku kugejja ng’etereeza ebifo ebikwata obusimu ebingi. Tekoma ku kugejja nnyo wabula erina n’ebizibu ebitonotono mu lubuto n’ekyenda. Okugatta ku ekyo, bw’ogeraageranya n’eddagala eddala eppya erikendeeza ku buzito, Retatrutid, ng’eddagala eriziyiza okugejja emirundi esatu, erina ekikolwa eky’amaanyi ennyo eky’okugejja n’omuwendo omunene ogw’abantu abakozesebwa.
Enkola ya Retatrutid ekola ki?
Enkola y’okukola kwa Retatrutid okusinga eva ku bikolwa byayo eby’ekika kya agonistic ku bikwata ebingi. Ekisooka, agonistic effect yaayo ku glucagon-like peptide-1 receptor (GLP-1R) eyongera ku kufulumya insulin, eziyiza okufulumya glucagon, ekendeeza ku glucose mu musaayi, ate mu kiseera kye kimu elwawo okufulumya amazzi mu lubuto, eyongera okukkuta, n’okukendeeza ku mmere [2] . Ekirala, agonistic effect yaayo ku glucose-dependent insulinotropic polypeptide receptor (GIPR) esobola okutumbula insulin secretion, okutumbula glucose utilization, era okuba n’akakwate ku fat metabolism, okuziyiza lipolysis n’okutumbula amasavu synthesis [2] . Ekirala, wadde ng’ekikolwa kya agonistic ekya Retatrutid ku glucagon receptor (GCGR) kitera okutumbula glycogenolysis ne gluconeogenesis mu kibumba, okwongera ku miwendo gya glucose mu musaayi, wansi w’ekikolwa kya Retatrutid, ekikolwa kino eky’okwongera ku glucose mu musaayi kikyusibwakyusibwa ebikolwa by’ebikwata ebirala ebibiri. Mu kiseera kye kimu, kitumbula okusasika kw’amasavu n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu [2] . Enkola eno ey’okukola erimu ebigendererwa ebingi eyinza okuba ennungi mu kujjanjaba omugejjo okusinga eddagala eriweweeza ku bulwadde buno (single receptor agonists).
Nga ekola mu kiseera kye kimu ebikwata bino ebisatu, Retatrutid esobola okukola ebikolwa eby’enjawulo ebifuga enkyukakyuka mu mubiri n’okukola ebikolwa eby’obujjanjabi ku mugejjo n’endwadde ezikwatagana nabyo. Mu nsonga z’okulungamya emiwendo gya glucose mu musaayi, olw’okukola kwa GLP-1R ne GIPR okutumbula okufulumya insulini n’okuziyiza okufulumya glucagon, n’okukola kwa GCGR nga kukyusibwakyusibwa ebiva mu bikolwa by’ebikwata ebirala ebibiri, Retatrutid esobola bulungi okutereeza emiwendo gya glucose mu musaayi, ekintu eky’amakulu mangi mu kujjanjaba enkyukakyuka y’emmere ey’ekika eky’okubiri [1, 2] . Mu nsonga y’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu, okukola kwa GCGR kutumbula lipolysis n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu. Mu kiseera kye kimu, okukola kwa GLP-1R kwongera okukkuta n’okukendeeza ku mmere, okwongera okukendeeza ku kusengejja amasavu [1, 2] . Okugatta ku ekyo, Retatrutid era erina akakwate ak’omugaso ku bulwadde bw’ekibumba obw’amasavu obutali bwa mwenge. Kisobola okukendeeza amasavu mu kibumba n’okulongoosa enkola y’ekibumba. Okugezesebwa okwa randomized, double-blind, placebo-controlled kwalaga nti enkyukakyuka eya wakati mu masavu g’ekibumba mu kibinja ky’abajjanjabi Retatrutid ku wiiki 24 yali wansi nnyo okusinga mu kibinja kya placebo [3]..
HbA1c, obuzito bw’omubiri, puleesa, n’amasavu Data zibeera least-squares means (nga zirina error bars eziraga SEs) okuva mu efficacy analysis set, okuggyako nga kiragiddwa bulala.
Ensibuko:PubMed [4] .
Retatrutid etereeza etya ddala enkyukakyuka ya glucose oluvannyuma lw’okukola ebikwata ku bitundu ebisatu?
Retatrutid etereeza glucose mu musaayi ng’eyita mu nkola eziwera, omuli okukola ku GLP-1 ne GIP receptors, okusitula okufulumya insulin, okuziyiza okufulumya glucagon, okulwawo okufulumya amazzi mu lubuto, okulungamya enkyukakyuka y’amasavu, n’okukendeeza ku miwendo gya ANGPTL3/8. Mu nsonga z’okulungamya glucose mu musaayi, Retatrutid ekola ku GLP-1 ne GIP receptors, okutumbula okuwuliziganya kw’obutoffaali bwa β obw’olubuto eri glucose, okukola n’okufulumya insulin, n’oluvannyuma okutumbula okutwalibwa n’okukozesa glucose mu bitundu by’omubiri, okutuuka ku kikolwa ky’okukendeeza glucose mu musaayi [4, 5] .Mu kunoonyereza ku balwadde b’ekika kya 2 metabolism, . Retatrutid yalaga ekikolwa ekinene eky’okukendeeza ku glycated hemoglobin (HbA1c), ekisinga okuganyulwa mu kifo kyayo mu kusitula okufulumya insulini (Rosenstock J, 2023). Mu kiseera kye kimu, okukola ekirungo kya GLP-1 kiyinza okuziyiza okufulumya glucagon obutoffaali bwa α obw’olubuto, ne kiziyiza glucose mu musaayi okubeera waggulu ennyo. Mu kunoonyereza ku bujjanjabi, kizuuliddwa nti emiwendo gya glucagon mu balwadde abakozesa Retatrutid gikendedde, ekiyamba okukuuma obutebenkevu bwa glucose mu musaayi [4, 5] . Okukola GLP-1 ne GIP receptors nakyo kiyinza okulwawo omutindo gw’okufulumya emmere mu lubuto, okukendeeza ku kugaaya n’okunyiga emmere, n’okukendeeza ku kulinnya okw’amaanyi okwa glucose mu musaayi oluvannyuma lw’okulya. Okunoonyereza kulaga nti obudde bw’okufulumya amazzi mu lubuto bw’abalwadde abajjanjabwa n’eddagala lya Retatrutid buwanvuwa nnyo oluvannyuma lw’okulya, bwe kityo ne kikendeeza ku muwendo gwa glucose mu musaayi ogw’oku ntikko oluvannyuma lw’okulya [4]..
Okulungamya enkyukakyuka y’amasavu nga Retatrutid nakyo kikosa enkyukakyuka ya glucose mu ngeri etali butereevu. Okugeza, mu kunoonyereza ku balwadde abagejjulukuka, kizuuliddwa nti Retatrutid esobola okukendeeza ku miwendo gya triglycerides (TG), low-density lipoprotein (LDL), ne very-low-density lipoprotein (VLDL) cholesterol [2, 6] . Okulongoosa kuno mu nkyukakyuka y’amasavu kuyinza okuba nga kwekuusa ku kulongoosa mu kuwulira kwa insulini, bwe kityo ne kiyamba mu kufuga glucose mu musaayi. Okusingira ddala, oluvannyuma lw’okujjanjabwa Retatrutid, asidi wa plasma 3-hydroxybutyric (3-HB) yeeyongera, nga ewerekerwako okweyongera kwa 3-hydroxybutyrylcarnitine (C 4OH), omugerageranyo gwa acetylcarnitine ku carnitine ow’eddembe (C 2/C 0), ne acylcarnitine ow’olujegere olw’omu makkati, ekiraga nti lipolysis eyongezeddwa mu bitundu by’amasavu n’okwesigamira okweyongera ku masavu okufuuka omukka (oxidation).
Retatrutid era esobola okukendeeza ku muwendo gwa dihydroceramides (DhCers) gwonna, era enkyukakyuka eno ekwatagana n’okulongoosa mu kuwulikika kwa insulini, okukendeeza ku hepatic steatosis, n’okuzimba mu nkola [6] .Mu kiseera kye kimu, Retatrutid era esobola okukendeeza ku bungi bw’ekirungo kya ANGPTL3/8 complex mu serum y’abalwadde ab’ekika kya 2 metabolism, okutereeza enkyukakyuka ya glucose [7] . ANGPTL3/8 ye ddagala erisinga okukola obulungi eriziyiza okutambula kw’omusaayi mu lipoprotein lipase (LPL), era omutindo gwayo mu musaayi gukwatagana butereevu ne TG ne low-density lipoprotein cholesterol (LDL-C). Retatrutid ekendeeza ku mutindo gwa ANGPTL3/8, eyinza okulungamya enkyukakyuka ya glucose nga ekendeeza ku lipoproteins ezirimu triglyceride [7]. .
Mu bintu ki Retatrutid mw’alaga ebivaamu?
Ekikulu ekiva mu kugejja:
Retatrutid eraga ebikolwa eby’amaanyi mu kugejja mu kugezesebwa okw’obujjanjabi okungi. Okugeza, mu kunoonyereza okwakolebwa mu bujjanjabi okwali kuzingiramu abantu abakulu 338 [2] , abalwadde abajjanjabwa ne dose ez’enjawulo eza Retatrutid baali bakendedde nnyo ku buzito ku wiiki 48. Mu bano, abalwadde mu kibinja kya ddoozi ya 12mg baalina okugejja kwa bitundu 24.2%, era ekitundu ekinene eky’abalwadde baatuuka ku kugejja ku diguli ez’enjawulo. Okugeza, mu balwadde abafuna dose ya 4mg, 8mg, ne 12mg, abalwadde 92%, 100%, ne 100% baakendeeza ku buzito bw’omubiri gwabwe ebitundu 5% oba okusingawo. Mu kunoonyereza okulala [8] , okugezesebwa okubiri okwakolebwa mu ngeri ey’ekifuulannenge okwali kuzingiramu abalwadde 353 ab’ekika kya 2 abakola ku nkyukakyuka y’emmere kwalaga nti bw’ogeraageranya n’eddagala eriyitibwa placebo, Retatrutid esobola okukendeeza ennyo ku buzito bw’omubiri gw’abalwadde ne kkiro 11.89 n’okukendeeza ku glycated hemoglobin (HbA1C). Okugatta ku ekyo, mu kugezesebwa okwakolebwa ku balwadde abakulu abagejjulukuka abatali ba ssukaali, Retatrutid yaleeta okugejja ebitundu 24.2% mu balwadde, ate abalwadde 83% ne bakendeeza ku buzito bw’omubiri gwabwe ebitundu 15% oba okusingawo ku wiiki 48. Ebivudde mu kunoonyereza kuno biraga nti Retatrutid erina obusobozi bungi mu kugejja.
Obujjanjabi bw'enkyukakyuka y'emmere ey'ekika kya 2 :
Retatrutid era eraga obusobozi obumu mu kujjanjaba enkyukakyuka y’omubiri ey’ekika eky’okubiri. Mu kugezesebwa okumu, Retatrutid eraga okukendeera mu glycated hemoglobin (HbA1c) n’okugejja okusinziira ku ddoozi. Okugeza, mu kunoonyereza okumu, mu balwadde b’ekika kya 2 metabolism, Retatrutid yalaga ekikolwa ekinene eky’okufuga glucose mu musaayi, okukendeeza ku glycated hemoglobin ne 1.64% bw’ogeraageranya ne placebo [4, 8] . Okugatta ku ekyo, mu kugezesebwa okwa randomized, double-blind, placebo, ne active-controlled parallel-group phase 2 trial, ebikolwa by’ebisolo ebirina type 2 metabolism byalaga okukendeera okw’amaanyi mu glycated hemoglobin levels n’okugejja okusinziira ku dose oluvannyuma lw’okufuna obujjanjabi bwa Retatrutid [4] . Kino kiyinza okuva ku bikolwa byonna eby’eddagala lino ku GLP-1, GCGR, ne GIPR, ebirongoosa enkyukakyuka ya glucose n’okutebenkeza amaanyi.
Okulongoosa mu bintu ebiyinza okuleeta akabi ku misuwa gy’omutima:
Retatrutid tesobola kukendeeza ku buzito bwa mubiri gwokka wabula n’okulongoosa ensonga z’obulabe eri emisuwa, gamba nga serum lipid profile ne glycated hemoglobin levels. Kino kiraga akakwate ak’okumpi mu pathophysiological wakati w’omugejjo n’endwadde z’emisuwa, era Retatrutid eyinza okulongoosa obulamu bw’emisuwa n’emisuwa gy’abalwadde abagejjulukuka okuyita mu makubo agawerako. Okugeza, okukendeeza ku miwendo egitali gya HDL-C, apoB, ne LDLP kiyinza okukendeeza ku bulabe bw’okuzimba emisuwa; okukendeeza ku miwendo gya glycated hemoglobin kiyinza okulongoosa okufuga glucose mu musaayi mu balwadde b’enkyukakyuka mu mubiri, bwe kityo ne kikendeeza ku bulabe bw’ebizibu by’emisuwa gy’omutima [8-10]. .
Obujjanjabi bw’obulwadde bw’ekibumba obutaliimu masavu (NAFLD):
Retatrutid ye peptide empya ey’okukwata ebitundu bisatu etunuulira ekirungo kya glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), n’ekirungo kya glucagon-like peptide-1 receptor (GLP-1R). Okunoonyereza kulaga nti Retatrutid erina obusobozi mu kujjanjaba obulwadde bw’ekibumba obw’amasavu obutali bwa mwenge. Mu kunoonyereza okumu, okugezesebwa okwa randomized, double-blind, placebo-controlled trial okwamala wiiki 48 kwakolebwa ku beetabye mu kugezesebwa abalina obulwadde bw’ekibumba obw’amasavu obukwatagana n’obutakola bulungi mu nkyukakyuka y’emmere n’amasavu mu kibumba aga ≥10%. Ebivuddemu biraga nti ku wiiki 24, enkyukakyuka eza wakati mu masavu g’ekibumba okusinziira ku ntandikwa mu beetabye mu kujjanjabwa ne dose ez’enjawulo eza Retatrutid (1mg, 4mg, 8mg, ne 12mg) zaali -42.9%, -57.0%, -81.4%, ne -82.4%, okusinziira ku, ate mu kibinja kya placebo yali +0.3% [3] . Kino kiraga nti Retatrutid eyinza okuba n’akakwate akakulu mu bujjanjabi ku bulwadde bw’ekibumba obw’amasavu obutali bwa mwenge.
Mu kumaliriza, nga novel triple receptor agonist, Retatrutid eraga obusobozi bungi mu kujjanjaba omugejjo n’endwadde ezikwatagana nabyo. Kiyinza okukola ekirungo kya glucagon, ekikwata insulinotropic polypeptide eyeesigama ku glucose, n’ekirungo kya glucagon-like peptide-1, okulungamya mu bujjuvu enkyukakyuka y’omubiri okuva mu bipimo ebingi, okulongoosa okufuga glucose mu musaayi, okukendeeza ku buzito bw’omubiri, n’okulungamya enkyukakyuka y’amasavu. Okuvaayo kwa Retatrutid kuleeta obujjanjabi obupya eri abalwadde abagejjulukuka, enkyukakyuka y’omubiri ey’ekika eky’okubiri, n’endwadde endala. Kisuubirwa okumenyawo obuzibu bw’eddagala ery’ekinnansi erya single receptor agonist, okuwa ekyokulwanyisa eky’amaanyi ennyo eky’okugonjoola ebizibu ebyeyongera okuba eby’amaanyi eby’omugejjo n’endwadde z’enkyukakyuka mu mubiri, okutumbula okwongera okukulaakulanya eby’obujjanjabi ebikwatagana nabyo, okutumbula omutindo gw’obulamu bw’abalwadde, n’okukendeeza ku buzito bw’obujjanjabi mu mbeera z’abantu.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Rosenstock J mukenkufu alina obuyinza bungi mu by’obusawo, ng’akolagana nnyo n’ebitongole nga University of Texas Southwestern Medical Center ne University of Texas Dallas. Akola n’okunoonyereza mu bifo nga Canadian VIGOR Center ne Veloc Clin Res Ctr Med City. Okunoonyereza kwe kukwata ku endocrinology and metabolism, cardiovascular system and cardiology, pharmacology, n’eddagala ery’okugezesa, ng’essira aliteeka ku metabolism, omugejjo, n’obujjanjabi obukwatagana nabyo n’okukola eddagala. J Rosenstock atuuse ku buwanguzi obw’amaanyi mu busawo obw’obujjanjabi, n’alondebwa okuba Highly Cited Researcher okuva mu 2017 okutuuka mu 2024. Kino kiraga nti omulimu gwe gukwata nnyo n’okusiimibwa mu bugazi. Ng’ayita mu nkolagana n’ebitongole by’okunoonyereza ebingi, avvuunudde bulungi ebizuuliddwa mu kunoonyereza okusookerwako mu kukozesebwa mu bujjanjabi, n’aganyula abalwadde abalina endwadde z’enkyukakyuka mu mubiri n’emisuwa n’okutumbula ssaayansi w’obusawo. Rosenstock J awandiikiddwa mu kiwandiiko ekijuliziddwa [4].
