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 ku ba Triple Agonists
Mu myaka egiyise, olw’okunoonyereza ku nsengekera y’endwadde z’enkyukakyuka mu mubiri okweyongera, okukola eddagala eriweweeza ku bulwadde buno (multi-target agonist drugs) erigenderera ebirungo ebikwata obusimu ebingi kifuuse omulamwa ogw’amaanyi. Retatrutid ye agonist ey’emirundi esatu empya ey’ebirungo ebikwata insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), n’ebikwata glucagon (GC) eyeesigama ku glucose.
(1) Omusingi gw’omubiri ogw’emirimu gy’ekirungo ekikwata obusimu
GIP Receptor: GIP ye hormone efulumya insulin mu byenda efulumizibwa obutoffaali bwa K mu kyenda ekitono, efuluma mangu oluvannyuma lw’okulya. Nga yesibye ku GIP receptor, GIP esitula okufulumya insulini, era ekikolwa kino eky’okusitula kisinziira ku glucose, ekitegeeza nti nga glucose mu musaayi bwe yeeyongera, GIP eyongera ku nkola yaayo ey’okufulumya insulini, ekiyamba okukuuma emiwendo gya glucose mu musaayi nga gitebenkedde. Okugatta ku ekyo, GIP yeetaba mu kulungamya enkyukakyuka y’amasavu, n’ekwata ku njawulo y’obutoffaali bw’amasavu n’okukuŋŋaanyizibwa kw’amasavu.
Ekifaananyi 1. Obujjanjabi bwa RETA oba SEMA bukendeeza ku buzito bw’omubiri n’okulongoosa glucose mu musaayi mu kisiibo.a Enkyukakyuka ku buli kikumi mu buzito bw’omubiri okuva ku ntandikwa zitegeezebwa. b, Epididymal white adipose tissue obuzito bwapimibwa ku nkomerero. c Glucose mu musaayi gw’okusiiba yapimibwa ku ntandikwa ne mu kunoonyereza kwonna mu biseera ebiragiddwa okutuuka ku nkomerero. d Okusimbuliza ebizimba oba 'okutwala ekizimba' kitegeezebwa.
GLP-1 receptor: GLP-1 efulumizibwa obutoffaali bwa L obw’ekyenda era era erina enkola ya insulinotropic eyesigamye ku glucose, okutumbula okukola insulini n’okufulumya, okuziyiza okufulumya glucagon, n’okukendeeza ku glucose efuluma mu kibumba. GLP-1 era alwawo okufulumya amazzi mu lubuto, eyongera okukkuta, era bw’atyo n’akendeeza ku mmere gy’olya. Kirina ebikolwa eby’obukuumi n’okukula ku butoffaali bwa beta obw’olubuto, ekiyamba okukuuma enkola y’olubuto.
3. Ekiwandiiko kya GC:
Oluvannyuma lw’okusiba ku GC receptor, glucagon okusinga ekola ku kibumba ng’etumbula glycogenolysis ne gluconeogenesis, bwe kityo n’esitula emiwendo gya glucose mu musaayi. Mu nkyukakyuka y’amasavu, kitumbula okusasika kw’amasavu, okwongera okufulumya n’okufuuka omukka gwa asidi z’amasavu okusobola okufuna amaanyi. Mu mbeera z’omubiri eza bulijjo, okufulumya glucagon kuziyizibwa nga glucose mu musaayi alinnye okukuuma glucose balance.
(2) Ebirungi ebiri mu Kikolwa kya Triple Agonist
Nga triple agonist, Retatrutid esobola okukola omulundi gumu receptors zino essatu, okukola synergistic effects. Nga ekola ku bikwata GIP ne GLP-1, eyongera ku kufulumya insulini eyeesigama ku glucose, mu ngeri ennungi n’ekendeeza ku muwendo gwa glucose mu musaayi. Okwongera okukkuta n’okulwawo okufulumya amazzi mu lubuto okuleetebwa okukola kwa GLP-1 receptor, awamu n’okusaanuuka kw’amasavu okutumbulwa okukola kwa GC receptor, byonna awamu biyamba mu kuddukanya obuzito. Enkola eno ey’okukola erimu ebigendererwa ebingi egaba okulungamya okusingawo okujjuvu okw’enkola ez’enjawulo ez’omubiri ezikwatagana n’endwadde z’enkyukakyuka mu mubiri.
Enkola y’Ekikolwa kya Retatrutid mu ndwadde z’enkyukakyuka mu mubiri
Endwadde z’enkyukakyuka mu mubiri ze kiraasi y’embeera ezireetebwa okutaataaganyizibwa mu nkola z’enkyukakyuka mu mubiri, omuli embeera eza bulijjo nga ssukaali, omugejjo, n’obulwadde bw’ekibumba obw’amasavu obutali bwa mwenge. Retatrutid ekola ebikolwa byayo ku ndwadde zino ez’okukyusakyusa emmere ng’eyita mu nkola yaayo ey’enjawulo ey’ekika kya triple agonist.
(1) Enkola y’Ekikolwa mu Ssukaali
Okulungamya Glucose: Retatrutid ekola GIP ne GLP-1 receptors, okutumbula okufulumya insulini eyesigamye ku glucose. Omuwendo gwa glucose mu musaayi bwe gulinnya, gusitula bulungi obutoffaali bwa beta obw’omu lubuto okufulumya insulini, ne kitumbula okutwalibwa n’okukozesa glucose, bwe kityo ne kikendeeza ku muwendo gwa glucose mu musaayi. Nga eziyiza okufulumya glucagon n’okukendeeza ku glucose afuluma mu kibumba, eyongera okutebenkeza emiwendo gya glucose mu musaayi. Mu kugezesebwa okw’obujjanjabi okwali kuzingiramu abalwadde ba sukaali ow’ekika eky’okubiri, obujjanjabi bwa Retatrutid bwavaamu okukendeeza ennyo ku muwendo gwa sukaali mu musaayi nga basiiba n’oluvannyuma lw’okulya.
Okukuuma obutoffaali bwa beta mu lubuto: Okukola kw’ekirungo kya GLP-1 tekikoma ku kutumbula kufulumya insulini wabula era kulina ekikolwa eky’obukuumi n’okukula ku butoffaali bwa beta obw’olubuto. Retatrutid eyinza okutuukiriza kino ng’ekola buli kiseera ekikwata kya GLP-1, n’ekendeeza ku kufa kw’obutoffaali bwa beta, n’eyongera ku muwendo gwazo n’enkola yazo, bwe kityo n’elongoosa obusobozi bw’okufulumya insulini n’okukuuma emiwendo gya glucose mu musaayi nga gitebenkedde okumala ebbanga eddene.
(2) Enkola y’okukola mu mugejjo
Okulungamya amaanyi agayingira: Retatrutid ekola ku bikwata GLP-1, n’elwawo okufulumya amazzi mu lubuto, n’ewangaaza obudde bw’okusigala ng’emmere mu lubuto, eyongera okukkuta, n’okukendeeza ku mmere gy’olya. Kiyinza okukola ku busimu obw’omu makkati okulung’amya obusimu obukwata ku kwagala okulya, gamba ng’okuziyiza okufulumya orexin, okwongera okukendeeza ku njagala y’okulya, era bwe kityo ne kifuga amaanyi agayingira.
Okwongera ku nsaasaanya y’amasoboza: Okukola kw’ekirungo kya GC kitumbula okusasika kw’amasavu, okwongera okufulumya n’okufuuka omukka gwa asidi z’amasavu okusobola okukola amaanyi. Okufuuka omukka gwa asidi z’amasavu kiwa omubiri amaanyi, kikendeeza ku kutereka amasavu, era kiyamba mu kugejja. Okukola kw’ekirungo kya GIP nakyo kyetaba mu kulungamya enkyukakyuka y’amasoboza, okwongera ku nsaasaanya y’amasoboza.
Ekifaananyi 2 Obujjanjabi bwa RETA bukendeeza ku buzito bw’omubiri n’amasavu, bulongoosa glucose mu musaayi mu kisiibo. a Enkyukakyuka ku buli kikumi mu buzito bw’omubiri okuva ku ntandikwa zitegeezebwa. b Epididymal white adipose tissue yapimibwa ku nkomerero ne zifuuka normaled okutuuka ku buzito bw’omubiri gwonna. c Glucose mu musaayi gw’okusiiba yapimibwa ku ntandikwa ne mu kunoonyereza kwonna mu biseera ebiragiddwa okutuuka ku nkomerero.
(3) Enkola y’okukola mu bulwadde bw’ekibumba obw’amasavu obutali bwa mwenge
Okulongoosa mu nkyukakyuka y’amasavu mu kibumba: Retatrutid ekola GC receptor, okutumbula okumenya n’okufuuka β-oxidation y’amasavu mu kibumba, bwe kityo n’ekendeeza ku kukuŋŋaanyizibwa kw’amasavu mu kibumba. Okukola kw’ebikwata GIP ne GLP-1 kuyinza okulungamya okwolesebwa kw’obuzaale obukwatagana n’enkyukakyuka y’amasavu mu kibumba, okulinnyisa okwolesebwa kw’ebitambuza asidi w’amasavu ne asidi w’amasavu oxidases, bwe kityo ne kitumbula okutwalibwa n’okufuuka asidi w’amasavu, n’okwongera okulongoosa enkyukakyuka y’amasavu mu kibumba.
Enhanced insulin sensitivity: Wadde nga erongoosa okulungamya glucose n’okwongera ku insulin secretion, Retatrutid esobola okutumbula hepatic insulin sensitivity nga ekola ku GLP-1 receptors. Okwongera okutegeera insulini kwongera ku ngeri ekibumba gye kiddamu insulini, ne kiziyiza bulungi okufuluma kwa glucose mu kibumba, ne kikendeeza ku kukola asidi w’amasavu mu ngeri ya de novo, era bwe kityo ne kikendeeza ku kuzimba kw’ekibumba.
Enkozesa n’ebikolwa bya Retatrutid mu ndwadde z’enkyukakyuka mu mubiri
(1) Okukozesebwa mu Ssukaali
lycemic Control Effects: Retatrutid eraga ebikulu ebiva mu kufuga glycemic mu balwadde ba sukaali ow’ekika eky’okubiri. Okusinziira ku biwandiiko, abalwadde abajjanjabiddwa Retatrutid baalaga okukendeera okw’amaanyi mu miwendo gya hemoglobin A1c (HbA1c). Mu kugezesebwa okwakolebwa mu ngeri ey’ekifuulannenge okwali kuzingiramu abalwadde 353 abalina ssukaali ow’ekika eky’okubiri, emiwendo gya HbA1c mu kibinja ky’abajjanjabi ba Retatrutid gyakendeera ebitundu 1.64% okuva ku ntandikwa, so nga tewali nkyukakyuka nnene mu kibinja kya placebo.
Okugerageranya n’eddagala eddala: Bw’ogeraageranya n’eddagala ery’ekinnansi eriweweeza ku ssukaali nga metformin oba GLP-1 receptor agonists, Retatrutid eraga nti ekola bulungi mu kufuga glucose mu musaayi.
(2) Okukozesebwa mu mugejjo
Ebiva mu kugejja: Retatrutid eraga nti ekola bulungi mu kujjanjaba omugejjo. Mu kugezesebwa okw’obujjanjabi okwagenderera abalwadde abakulu abagejjulukuka, okugejja okw’amaanyi kwalabiddwa oluvannyuma lwa wiiki 48 nga bajjanjabwa ne dose ez’enjawulo eza Retatrutid. Mu kugezesebwa okumu, abalwadde abajjanjabwa ne ddoozi ya Retatrutid eya 12mg baafuna okugejja kwa wakati wa 24.2% oluvannyuma lwa wiiki 48, bw’ogeraageranya n’ebitundu 2.1% byokka mu kibinja kya placebo. Okugatta ku ekyo, 83% ku beetabye mu kibinja ekya dose ennene baatuuka ku kugejja ebitundu 15% oba okusingawo, nga kino kyasukka nnyo omuwendo gwa 2% mu kibinja kya placebo.
Ebikosa okumala ebbanga eddene: Retatrutid ekuuma bulungi ebikolwa by’okugejja mu kiseera kyonna eky’obujjanjabi. Kino kiraga nti okukozesa okumala ebbanga eddene kiyinza okuyamba okukuuma omugejjo nga gutebenkedde n’okuziyiza okuddamu okugejja, ekintu eky’omugaso mu kuddukanya omugejjo okumala ebbanga eddene.
(3) Okukozesebwa mu bulwadde bw’ekibumba obw’amasavu obutali bwa mwenge
Okukendeeza amasavu mu kibumba: Mu balwadde abalina obulwadde bw’amasavu mu kibumba obukwatagana n’obutakola bulungi mu mubiri n’amasavu mu kibumba ≥10%, obujjanjabi bwa Retatrutid bwavaamu okukendeeza ennyo ku masavu mu kibumba. Mu kugezesebwa okwa randomized, double-blind, placebo-controlled trial, ku wiiki 24, amasavu mu kibumba gakendeera ebitundu 81.4% ne 82.4% okuva ku ntandikwa mu bibinja bya dose ya 8 mg ne 12 mg, okusinziira ku, ate ekibinja kya placebo kyakendeera ebitundu 0.3% byokka.
Ebirungi n’obusobozi bwa Triple Agonist
Retatrutid etereeza mu bujjuvu amakubo amangi aga pathophysiological ag’endwadde z’enkyukakyuka mu mubiri nga ekola mu kiseera kye kimu GIP, GLP-1, ne GC receptors. Okuva ku kufuga glucose mu musaayi, okuddukanya obuzito, okutuuka ku kulongoosa mu nkyukakyuka y’amasavu mu kibumba, enkola eno ey’okukola erimu ebigendererwa ebingi mu ndowooza etuwa okutereeza okujjuvu ennyo okw’obuzibu bw’enkyukakyuka mu mubiri bw’ogeraageranya n’eddagala erigendererwamu ekimu, nga kiraga obusobozi okukola ku nsonga enzibu ezivaako endwadde z’enkyukakyuka mu mubiri. Ebiwandiiko ebikwata ku kugezesebwa kw’obujjanjabi ebiriwo biraga nti Retatrutid etuuse ku bikolwa eby’amaanyi mu kujjanjaba endwadde z’enkyukakyuka mu mubiri nga ssukaali, omugejjo, n’obulwadde bw’ekibumba obw’amasavu obutali bwa mwenge.
Mu bufunzi
Nga novel triple agonist, Retatrutid alina ekisuubizo mu kujjanjaba endwadde z’enkyukakyuka mu mubiri.
Ensonda
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[2] Kaur M, Misra S. Okuddamu okwetegereza eddagala erinoonyereza erya retatrutide, ekirungo ekipya eky’ekika kya triple agonist ekijjanjaba omugejjo[J]. European Journal of Clinical Pharmacology, 2024,80 (5): 669-676.DOI: 10.1007 / s00228-024-03646-0.
[3] Lopez D. C., Pajimna J. T., Milan M. D., n’abalala. 7792 Obulung’amu bwa Retatrutid okukendeeza ku buzito n’ebikosa byayo mu mutima mu bantu abakulu: Okwekenenya okutegekeddwa n’okwekenneenya okutambula[J]. Journal of the Endocrine Society, 2024,8 (Supplement_1): bvae163-bvae749.DOI: 10.1210 / jendso / bvae163.749.
[4] Jastreboff A. M., Kaplan L. M., Frías J. P., n’abalala. Triple-Hormone-Receptor Agonist Retatrutid ku mugejjo - Okugezesebwa okw'omutendera ogw'okubiri[J]. New England Journal of Eddagala, 2023,389 (6): 514-526.DOI: 10.1056 / NEJMoa2301972.
[5] Doggrell S A. Retatrutide (LY3437943), eddagala eriziyiza GLP-1, GIP, ne glucagon receptor ddaala erigenda mu maaso mu kujjanjaba ssukaali n’omugejjo?[J]. Endowooza y'abakugu ku ddagala erinoonyereza, 2023,32 (5): 355-359.DOI:10.1080/13543784.2023.2206560.
Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
