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EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA BYOKKA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu kisenge (in vitro research) (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.
Okutwalira awamu
Maz ddagala ddene erikola nga agonist ya mirundi ebiri eri glucagon-like peptide-1 (GLP-1) ne glucagon receptors. GLP-1 ne glucagon receptors zikola emirimu emikulu mu kulungamya enkyukakyuka mu mubiri gw’omuntu. GLP-1 okusinga efulumizibwa obutoffaali bwa L mu kyenda, n’efulumizibwa oluvannyuma lw’okulya, era esitula okufulumya insulini mu ngeri eyeesigama ku bungi bwa glucose ate ng’eziyiza okufulumya glucagon, bwe kityo n’ekendeeza ku muwendo gwa glucose mu musaayi. GLP-1 era ekendeeza ku kufulumya amazzi mu lubuto, eyongera okukkuta, n’okukendeeza ku mmere gy’olya, bwe kityo n’eyamba mu kukendeeza ku buzito. Ebikwata glucagon okusinga bye bitereeza bbalansi ya glucose mu musaayi. Oluvannyuma lwa glucagon okwesiba ku receptor yaayo, ekola amakubo agawerako ag’okukyusa obubonero okutumbula glycogenolysis ne gluconeogenesis, bwe kityo n’eyongera ku miwendo gya glucose mu musaayi. Maz, nga dual agonist, etuuka ku metabolic regulation okuyita mu nkola entegefu ey’okukwatagana.
Enkola y’Ekikolwa
Enkola y’okulungamya glucose mu musaayi
Okutumbula Okufuluma kwa Insulin: Oluvannyuma lw’okusiba ku GLP-1 receptor, Maz ekola amakubo g’obubonero wansi, omuli n’ekkubo ly’obubonero erya cAMP-PKA. Okukola kw’ekkubo lino kwongera ku buwulize bw’obutoffaali bwa β obw’olubuto eri glucose, ekivaako okulinnyisa okulaga kw’obuzaale bwa insulini n’okwongera ku kusengejja n’okufulumya insulini. Gsukaali bw’alinnya, Maz esobola bulungi okusitula okufulumya insulini, bw’atyo n’ekendeeza ku muwendo gwa glucose mu musaayi. Mu balwadde abalina enkyukakyuka y’omubiri ey’ekika kya 2, Maz eyongera ku kufulumya insulini oluvannyuma lw’okulya ng’eyita mu nkola eno, ekiyamba okukuuma emiwendo gya glucose mu musaayi nga gitebenkedde.
Okuziyiza okufulumya glucagon: Ekikolwa kya Maz ku bikwata glucagon nakyo kikwata ku kufulumya glucagon. Nga yesiba ku bikwata glucagon, eziyiza okukyusakyusa obubonero mu butoffaali bwa α obw’olubuto, ekikendeeza ku kusengejja glucagon n’okufulumya. Kino kiziyiza glycogenolysis ne gluconeogenesis, okukendeeza ku kukola glucose ku nsibuko n’okwongera okuyamba mu kukendeeza glucose mu musaayi. Okulungamya kuno okw’emirundi ebiri okw’okufulumya insulini ne glucagon kiwa Maz enkizo ey’amaanyi mu kulungamya glucose mu musaayi, okusobozesa okufuga obulungi emiwendo gya glucose mu musaayi n’okwewala enkyukakyuka ennene.
Ebitundu ku kikumi enkyukakyuka okuva ku ntandikwa mu buzito bw’omubiri okumala ekiseera. Ekitundu ky‟abeetabye mu kutendekebwa okutuuka ku biruubirirwa by‟okugejja.
Enkola y’okuddukanya obuzito
Okulungamya okwagala okulya: Maz yeekwata ku bikwata GLP-1, n’ekola obusimu obuyitibwa neurons mu kifo ekitereeza appetite mu hypothalamic appetite center. Obusimu buno bwetaba mu kutambuza obubonero bw’okukkuta, era ekikolwa kya Maz kyongera ku bubonero buno, bwe kityo ne kikendeeza ku mmere gye balya. Era kiyinza okukosa okufulumya obusimu bw’omu lubuto, gamba nga ghrelin, okwongera okutereeza okwagala okulya. Mu kugezesebwa okw’obujjanjabi, abeetabye mu kugezesebwa nga bakozesa Maz baategeezezza nti okwagala okulya kwakendeera n’emmere gye balya buli lunaku, ekivaako okugejja.
Okwongera ku nsaasaanya y’amaanyi: Maz era eyinza okutumbula okugejja ng’ekwata ku nkyukakyuka y’amaanyi mu mubiri. Okunoonyereza kulaga nti eyinza okukola ebitundu by’amasavu ebya kitaka, n’eyongera ku mirimu gyayo egy’obugumu. Ebitundu by’amasavu ebya kitaka birimu mitochondria bingi era bisobola okukozesa amaanyi okuyita mu thermogenesis etali ya kukankana. Maz eyinza okulungamya amakubo g’obubonero agakwatagana okutumbula okwawukana n’okukola kw’obutoffaali bw’amasavu obwa kitaka, n’eyongera ku busobozi bwabyo obw’okukola ebbugumu, bwe kityo n’eyongera ku nsaasaanya y’amaanyi g’omubiri n’okutuuka ku kugejja. Maz era ayinza okukwata ku nkyukakyuka y’amasavu amazungu, okutumbula okukyusa amasavu amazungu okufuuka amasavu aga kitaka, okwongera okulongoosa enkyukakyuka y’amasavu n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu.
Enkola y’okulungamya asidi wa Uric
Okulungamya okwolesebwa kw’obuzaale: Mu kunoonyereza nga bakozesa enkola y’envunza ey’obulwadde bwa hyperuricemia, enkyukakyuka ennene mu kwolesebwa kw’obuzaale obumu obukulu zaalabiddwa oluvannyuma lw’okuyingira mu nsonga za Maz. Enkyukakyuka zino mu kwolesebwa kw’obuzaale ziyinza okutuuka ku kukendeera mu miwendo gya asidi wa uric nga zitereeza ebisookerwako mu kukola asidi wa uric n’okwetaba mu nkola nga okukyusakyusa glycolipid n’okukyusakyusa purine. Obuzaale obulung’amibwa waggulu butumbula okufulumya asidi wa uric oba okwetaba mu makubo g’enkyukakyuka mu mubiri agaziyiza okukola asidi wa uric, ate obuzaale obulung’amibwa wansi bukendeeza ku kukola ebisookerwako okukola asidi wa uric, bwe kityo ne kikendeeza mu bujjuvu emiwendo gya asidi wa uric mu musaayi.
Okulungamya ekkubo ly’enkyukakyuka mu mubiri: Okwekenenya ebiwandiiko by’ekibumba kwalaga nti okuyingira mu nsonga za Maz kwagaggawaza nnyo amakubo ga KEGG omuli okufulumya entuuyo, enkola ya renin-angiotensin, enkyukakyuka ya histidine, okuziyiza platinum, ennyiriri z’obutoffaali obukola omusaayi, complement, n’okuzimba omusaayi. Okulungamya amakubo gano kuyinza okukwata mu ngeri etali butereevu mu nkyukakyuka ya asidi wa uric. Okulungamya ekkubo ly’okufulumya amazzi mu ntuuyo kuyinza okukosa enkyukakyuka ya asidi w’entuuyo, ekikwatagana ennyo n’enkyukakyuka y’amasavu. Enkyukakyuka mu nkyukakyuka y’amasavu ziyinza okukosa okukola n’okufulumya asidi wa uric. Okulungamya enkola ya renin-angiotensin kuyinza okukosa hemodynamics y’ekibumba n’enkola ya tubular, bwe kityo ne kikwata ku kuddamu okunyiga n’okufulumya asidi wa uric.
Obulung’amu
Enkola y’okufuga glucose
Mu kugezesebwa okwa randomized, double-blind, placebo-controlled Phase 2 clinical trial mu balwadde abalina type 2 metabolism, Maz yalaga ebikolwa ebinene eby’okufuga glucose mu musaayi. Okunoonyereza kuno kwalonda abalwadde abakulu abalina ekika kya 2 metabolism okufuna 3 mg, 4.5 mg, oba 6 mg ya Maz, 1.5 mg ya open-label dulaglutide, oba placebo, era ne baweebwa empiso wansi w’olususu okumala wiiki 20. Ebivuddemu biraga nti okuva ku ntandikwa okutuuka mu wiiki 20, enkyukakyuka eya wakati mu hemoglobin A1c (HbA1c) mu bibinja bya Maz yali wakati wa -1.41% okutuuka ku -1.67%, ate ekibinja kya dulaglutide kyalina enkyukakyuka ya -1.35% ate ekibinja kya placebo kyalina enkyukakyuka ya 0.03%. Bw’ogeraageranya n’ekibinja kya placebo, enkyukakyuka mu miwendo gya HbA1c mu bibinja byonna ebya ddoozi ya Maz zaali za maanyi mu bibalo (zonna P < 0.0001). Kino kiraga nti Maz ekola nnyo okusinga placebo mu kukendeeza ku miwendo gya HbA1c mu balwadde abalina ekika kya 2 metabolism, era egeraageranyizibwa oba n’okusinga dulaglutide. Okukendeera kw’emiwendo gya HbA1c kulaga obusobozi bwa Maz okulongoosa obulungi okufuga glycemic okumala ebbanga eddene mu balwadde, bwe kityo ne kikendeeza ku bizibu ebitawona ebya sukaali.
Ebiva mu kugejja
Maz eraga obulungi obw’amaanyi mu kuddukanya obuzito. Mu kunoonyereza okwatunuulidde abantu abakulu abagejjulukuka oba abagejjulukuka, wiiki 24 ez’obujjanjabi bwa Maz zalaga nti zikola bulungi mu kugejja. Abantu abakulu abagejjulukuka (body mass index [BMI] ≥24 kg/m²) abalina polyphagia ne/oba waakiri comorbidity emu eyeekuusa ku mugejjo, oba abantu abakulu abagejjulukuka (BMI ≥28 kg/m²), baaweebwa mu ngeri ey’ekifuulannenge (3:1:3:1:3:1) okufuna buli wiiki Maz 3mg, 4.5mg, 6mg, oba okukwatagana obujjanjabi bwa placebo. Ebivuddemu biraga nti okuva ku ntandikwa okutuuka mu wiiki 24, enkyukakyuka mu buzito mu kitundu kya wakati yali -6.7% (standard error 0.7) mu kibinja kya Maz 3 mg, -10.4% (0.7) mu kibinja kya 4.5 mg, -11.3% (0.7) mu kibinja kya 6 mg, ne 1.0% (0.7) mu kibinja kya placebo. Bw’ogeraageranya ne placebo, enjawulo mu bujjanjabi bwa Maz mu bibinja byonna ebya dose zaali wakati wa -7.7% okutuuka ku -12.3% (zonna P < 0.0001). Kino kiraga nti Maz esobola okukendeeza ennyo ku buzito bw’omubiri mu bantu abakulu abagejjulukuka oba abagejjulukuka mu ngeri eyesigamiziddwa ku ddoozi. Okugejja kuno tekukoma ku kuyamba kulongoosa ndabika y’omubiri gw’abalwadde wabula ekisinga obukulu kikendeeza ku bulabe bw’endwadde ez’enjawulo ezeekuusa ku mugejjo, gamba ng’endwadde z’emisuwa n’enkyukakyuka mu mubiri.
Ekikolwa ekikendeeza asidi wa Uric
Mu nkola y’envunza ey’obulwadde bwa hyperuricemia, Maz yalaga ebikolwa ebirungi eby’okukendeeza asidi wa uric. Hyperuricemia yaleetebwa mu nvunza nga baweebwa adenine ne potassium oxinic acid mu kamwa, oluvannyuma ne bajjanjabwa ne dose ez’enjawulo eza Maz. Ebivuddemu biraga nti ebibinja bya Maz ebya ddoozi eya wakati n’eya waggulu (0.05 mg/kg ne 0.075 mg/kg, ebiweebwa nga biyita mu mpiso wansi w’olususu buli luvannyuma lwa nnaku 3) byakendeeza nnyo ku muwendo gwa serum uric acid (SUA) mu nvunza. Maz era yalongoosa enkola y’ekibumba, yakendeeza ku serum creatinine (SCr) ne urine protein (U-Pro) levels, n’okulongoosa endwadde z’ebitundu by’ekibumba. Kino kiraga nti Maz tekoma ku kukendeeza ku muwendo gwa uric acid mu musaayi wabula erina n’ekikolwa eky’obukuumi ku kwonooneka kw’ekibumba okuva ku hyperuricemia.
Ebitundu by’Okusaba
Obujjanjabi bw’enkyukakyuka y’ebirungo ey’ekika kya 2
Okusinziira ku ngeri Maz gy’ekola ennyo mu kufuga glucose mu musaayi, erina obusobozi bungi okukozesebwa mu kujjanjaba enkyukakyuka y’omubiri ey’ekika eky’okubiri. Mu kiseera kino, obujjanjabi bw’enkyukakyuka y’emmere ey’ekika eky’okubiri okusinga bwesigamye ku kugatta eddagala eringi okufuga emiwendo gya glucose mu musaayi n’okuziyiza ebizibu okubaawo. Nga novel dual receptor agonist, enkola ya Maz ey’enjawulo ey’okukola egisobozesa okulungamya enkyukakyuka ya glucose ku mitendera mingi, nga egaba enkola empya ey’obujjanjabi eri abalwadde abalina enkyukakyuka y’omubiri ey’ekika eky’okubiri. Bw’ogeraageranya n’eddagala ly’ekinnansi eriweweeza ku ssukaali, Maz tekoma ku kukendeeza bulungi ku mutindo gwa glucose mu musaayi wabula era etuwa omugaso gw’okukendeeza ku buzito, ekintu ekikulu ennyo naddala eri abalwadde abasinga obungi abakola ku nkyukakyuka y’emmere ey’ekika kya 2 abagejjulukuka oba abagejjulukuka.
Okuddukanya omugejjo n’okugejja ennyo
Omugejjo n’omugejjo bifuuse ensonga z’ebyobulamu mu nsi yonna ezikwatagana ennyo n’okutandika kw’endwadde ez’enjawulo ezitawona. Ebikulu Maz by’ekola mu kuddukanya omugejjo bigifuula eky’obujjanjabi ekiyinza okuweebwa abantu abagejjulukuka n’abagejjulukuka. Nga etereeza okwagala okulya n’okwongera ku nsaasaanya y’amaanyi, Maz esobola okuyamba abalwadde abagejjulukuka n’abagejjulukuka okugejja n’okulongoosa embeera y’omubiri gwabwe. Bw’ogeraageranya n’enkola z’ekinnansi ez’okugejja nga okukola endya n’okukola dduyiro, Maz ekuwa obujjanjabi obw’obuyambi obusingako obulungi naddala eri abo abalwana okutuuka ku buzito bwabwe obutuufu nga bayita mu kuyingirira mu bulamu. Okugatta ku ekyo, olw’enkola yaayo ey’okukola erimu enkola eziwera ez’okulungamya omubiri, Maz eyinza okuba n’ebikosa ebirungi ku nkola z’emisuwa n’enkyukakyuka mu mubiri ate ng’ekendeeza ku buzito, bwe kityo n’ekendeeza ku bulabe bw’ebizibu ebiva ku mugejjo.
Mu bufunzi
Mu bufunze, nga novel dual agonist of GLP-1 ne glucagon receptors, Maz eraga enkola ez’enjawulo ez’okukola n’obulungi obw’amaanyi mu kulungamya glucose mu musaayi, okuddukanya obuzito, n’okulungamya okuyinza okubaawo kwa uric acid, nga ekola kinene nnyo mu kuddukanya ekika kya 2 metabolism, omugejjo, n’embeera z’omugejjo omungi.
Ensonda
[1] Zhang B, Cheng Z, Chen J, n’abalala. Obulung’amu n’obukuumi bwa Maz mu balwadde b’Abachina abalina enkyukakyuka y’ebirungo ey’ekika kya 2: Okugezesebwa okwa Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial[J]. Okulabirira okukyusakyusa emmere, 2024, 47 (1): 160-168.DOI: 10.2337 / dc23-1287.
[2] Nalisa D. L., Cuboia N., Dyab E., n’abalala. Obulung’amu n’obukuumi bwa Maz ku kugejja mu balwadde ba ssukaali n’abatali ba ssukaali: okwekenneenya okutegekeddwa n’okwekenneenya okugezesebwa okufugibwa okutali kwa bulijjo[J]. Ensalo mu Endocrinology, 2024,15. https://api.semanticscholar.org/CorpusID:267984513. Enkola y’okukuuma obutonde bw’ensi
[3] Ji L, Jiang H, Cheng Z, n’abalala. A phase 2 randomized controlled trial of mazdutide mu China abantu abakulu abagejjulukuka oba abantu abakulu abalina omugejjo[J]. Empuliziganya y’obutonde, 2023, 14 (1): 8289.DOI: 10.1038 / s41467-023-44067-4.
[4] Jiang H, Zhang Y, REN Y S. 77-LB: Ekipya Glucagon-Like Peptide-1 (GLP-1R) ne Glucagon (GCGR) Receptor Dual Agonist, Maz (IBI362), Akendeeza ku Hyperuricemia mu Nvunza ezirina Hyperuricemic[J]. Enkyukakyuka mu mubiri, 2023. https://api.semanticscholar.org/CorpusID:259452040
Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
