Bya Cocer Peptides 
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EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (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.
Okulambika okutwaliza awamu
Mazdutide 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 byenda, n’efulumizibwa oluvannyuma lw’okulya, era esitula okufulumya insulini mu ngeri eyeesigama ku bungi bwa glucose ate ng’eziyiza okufulumya glucagon, bwe kityo ne kikendeeza 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 omuddirirwa gw’amakubo g’okukyusa obubonero okutumbula glycogenolysis ne gluconeogenesis, bwe kityo n’eyongera ku miwendo gya glucose mu musaayi. Mazdutide, nga dual agonist, etuuka ku kulungamya metabolic okuyita mu nkola entegefu ey’okukwatagana.
Enkola y’Ekikolwa
Enkola y’okulungamya glucose mu musaayi
Okutumbula Okufulumya Insulin: Oluvannyuma lw’okusiba ku GLP-1 receptor, Mazdutide ekola amakubo g’obubonero wansi, omuli n’ekkubo ly’obubonero erya cAMP-PKA. Okukola ekkubo lino kwongera ku buwulize bw’obutoffaali bwa β obw’olubuto eri glucose, ekivaako upregulation of insulin gene expression n’okwongera ku insulin synthesis and secretion. Gsukaali bw’alinnya, Mazdutide asobola bulungi okusitula okufulumya insulini, bw’atyo n’akendeeza ku muwendo gwa glucose mu musaayi. Mu balwadde ba sukaali ow’ekika eky’okubiri, Mazdutide ayongera ku kufulumya insulini oluvannyuma lw’okulya ng’ayita mu nkola eno, ekiyamba okukuuma omutindo gwa glucose mu musaayi nga gutebenkedde.
Okuziyiza okufulumya glucagon: Ekikolwa kya mazdutide 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 Mazdutide 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: Mazdutide yeekwata ku bikwata GLP-1, n’ekola obusimu obuyitibwa neurons mu kifo ekitereeza appetite eya hypothalamic. Obusimu buno bwetaba mu kutambuza obubonero bw’okukkuta, era ekikolwa kya Mazdutide 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 mu malwaliro, abeetabye mu kugezesebwa nga bakozesa Mazdutide baategeeza nti okwagala okulya kwakendeera n’okukendeera kw’emmere gye balya buli lunaku, ekivaako okugejja.
Okwongera ku nsaasaanya y’amaanyi: Mazdutide 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. Mazdutide 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 mu mubiri n’okutuuka ku kugejja. Mazdutide 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 ez’amaanyi mu kwolesebwa kw’obuzaale obumu obukulu zaalabiddwa oluvannyuma lw’okuyingira mu nsonga za Mazdutide. 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 Mazdutide 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 entuuyo 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 ba sukaali ow’ekika eky’okubiri, Mazdutide yalaga ebikolwa ebinene eby’okufuga glucose mu musaayi. Okunoonyereza kuno kwalonda abalwadde abakulu abalina ssukaali ow’ekika eky’okubiri mu ngeri ey’ekifuulannenge okufuna 3 mg, 4.5 mg, oba 6 mg za Mazdutide, 1.5 mg eza 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 Mazdutide 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 dose ya Mazdutide zaali za maanyi mu bibalo (zonna P < 0.0001). Kino kiraga nti Mazdutide ekola nnyo okusinga placebo mu kukendeeza ku miwendo gya HbA1c mu balwadde ba sukaali ow’ekika eky’okubiri, era egeraageranyizibwa oba n’okusinga dulaglutide. Okukendeera kw’emiwendo gya HbA1c kulaga obusobozi bwa Mazdutide okulongoosa obulungi okufuga glycemic okumala ebbanga eddene mu balwadde, bwe kityo ne kikendeeza ku bizibu ebitawona ebya sukaali.
Ebiva mu kugejja
Mazdutide eraga obulungi obw’amaanyi mu kuddukanya obuzito. Mu kunoonyereza okwatunuulidde abantu abakulu abagejjulukuka oba abagejjulukuka, wiiki 24 ez’obujjanjabi bwa Mazdutide 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 Mazdutide 3mg, 4.5mg, 6mg, buli wiiki, 4.5mg, 6mg, buli wiiki. oba obujjanjabi bwa placebo obukwatagana. Ebivuddemu biraga nti okuva ku ntandikwa okutuuka mu wiiki 24, enkyukakyuka mu buzito mu kitundu kya wakati yali -6.7% (ensobi eya mutindo 0.7) mu kibinja kya Mazdutide 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 Mazdutide mu bibinja byonna ebya ddoozi zaali wakati wa -7.7% okutuuka ku -12.3% (zonna P < 0.0001). Kino kiraga nti Mazdutide 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 ya balwadde wabula ekisinga obukulu kikendeeza ku bulabe bw’endwadde ez’enjawulo ezeekuusa ku mugejjo, gamba ng’endwadde z’emisuwa ne ssukaali.
Ekikolwa ekikendeeza asidi wa Uric
Mu nkola y’envunza ey’obulwadde bwa hyperuricemia, Mazdutide yalaga ebikolwa ebirungi eby’okukendeeza asidi wa uric. Obulwadde bwa Hyperuricemia bwaleetebwa mu nvunza nga baweebwa adenine ne potassium oxinic acid mu kamwa, oluvannyuma ne bajjanjabwa ne dose ez’enjawulo eza Mazdutide. Ebivuddemu biraga nti ebibinja bya Mazdutide ebya ddoozi eya wakati n’eya waggulu (0.05 mg/kg ne 0.075 mg/kg, eweebwa nga bayita mu mpiso wansi w’olususu buli luvannyuma lwa nnaku 3) byakendeeza nnyo ku muwendo gwa serum uric acid (SUA) mu nvunza. Mazdutide 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 Mazdutide tekoma ku kukendeeza ku muwendo gwa uric acid mu musaayi wabula alina n’ekikolwa eky’obukuumi ku kwonooneka kw’ekibumba okuva ku hyperuricemia.
Ebitundu by’Okusaba
Obujjanjabi bwa Ssukaali ow’ekika eky’okubiri
Okusinziira ku bulungibwansi bwa Mazdutide mu kufuga glucose mu musaayi, erina obusobozi bungi okukozesebwa mu kujjanjaba ssukaali ow’ekika eky’okubiri. Mu kiseera kino, obujjanjabi bwa sukaali ow’ekika eky’okubiri okusinga bwesigamye ku kugatta eddagala eringi okufuga omuwendo gwa sukaali mu musaayi n’okuziyiza ebizibu okubaawo. Nga novel dual receptor agonist, enkola ya Mazdutide ey’enjawulo ey’okukola egisobozesa okulungamya enkyukakyuka ya glucose ku mitendera mingi, nga egaba enkola empya ey’obujjanjabi eri abalwadde ba sukaali ow’ekika eky’okubiri. Bw’ogeraageranya n’eddagala ly’ekinnansi eriweweeza ku ssukaali, Mazdutide tekoma ku kukendeeza bulungi ku mutindo gwa glucose mu musaayi wabula era etuwa omugaso gw’okukendeeza ku buzito, ekintu ekikulu naddala eri abalwadde ba sukaali ab’ekika eky’okubiri abasinga obungi 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 Mazdutide by’akola mu kuddukanya omugejjo bigifuula eddagala eriyinza okujjanjaba abantu abagejjulukuka n’abagejjulukuka. Nga etereeza okwagala okulya n’okwongera ku nsaasaanya y’amaanyi, Mazdutide esobola okuyamba abalwadde abagejjulukuka n’abagejjulukuka okugejja n’okulongoosa embeera y’omubiri gwabwe. Bw’ogeraageranya n’enkola z’ekinnansi ez’okugejja ng’okukola emmere n’okukola dduyiro, Mazdutide 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, Mazdutide 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 and glucagon receptors, Mazdutide eraga enkola ez’enjawulo ez’okukola n’obulungi obw’amaanyi mu kulungamya glucose mu musaayi, okuddukanya obuzito, n’okulungamya asidi wa uric ayinza okubaawo, ng’akola kinene nnyo mu kuddukanya ssukaali ow’ekika eky’okubiri, omugejjo, n’embeera z’omugejjo omungi.
Ensonda
[1] Zhang B, Cheng Z, Chen J, n’abalala. Obulung’amu n’obukuumi bwa Mazdutide mu balwadde b’Abachina abalina sukaali ow’ekika eky’okubiri: Okugezesebwa okwa Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial[J]. Okulabirira obulwadde bwa sukaali, 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 Mazdutide 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: Omupya Glucagon-Like Peptide-1 (GLP-1R) ne Glucagon (GCGR) Receptor Dual Agonist, Mazdutide (IBI362), Akendeeza ku Hyperuricemia mu Nvunza ezirina Hyperuricemic[J]. Ssukaali, 2023. Enkola y’okukuuma obutonde bw’ensi mu bitundu by’eggwanga eby’enjawulo
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