Ekirungo kya Retatrutid (GLP-3) 10mg

▎ Enzimba ya GLP-3

▎ Ensibuko ya Molekyulu

GLP-3 (LY3437943) ye peptide ey’okunoonyereza eyogerwako nga agonist ey’okukwata ebitundu bisatu ku glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), ne glucagon receptor (GCGR).[1,2]

Ekifaananyi1. Schematic representation of the three receptor pathways eziteeseddwako ku GLP-3 mu kwekenneenya okujuliziddwa.[1]

Enkulaakulana mu kunoonyereza

Coskun, Tamer, ne banne baanoonyereza ku GLP-3 mu mbeba eza C57/Bl6 diet-induced obesity (DIO). Abawandiisi bano baategeeza enkyukakyuka ezisinziira ku ddoozi mu buzito bw’omubiri, kalori z’olya, ebirungo by’omubiri, glucose mu musaayi, insulini, ALT, ne triglycerides mu kibumba. Okugezesa okulala mu kunoonyereza kwe kumu kwakozesebwa okwekenneenya omugabo gwa GCGR, GIPR, ne GLP-1R signaling ku observed preclinical responses.[2]

Ekifaananyi2. Obuzito bw’omubiri, calorie-intake, body-composition, ne metabolic endpoints zaloopebwa ku LY3437943 mu mbeba ennene ennyo ezireetebwa emmere.[2]

Ebibe ebinene ennyo ebyava ku mmere byafuna dose ezirinnya omulundi gumu buli lunaku (QD) eza LY3437943 okumala ennaku 21 mu kunoonyereza okwayogerwako.

(A) Enkyukakyuka mu bitundu ku kikumi mu buzito bw’omubiri okumala ekiseera.

(B) Kalori ezikuŋŋaanyiziddwa mu bbanga.

(C – F) Enkyukakyuka mu butonde bw’omubiri mu gram ku nkomerero y’okunoonyereza: obuzito bw’omubiri (C), obuzito bw’amasavu (D), obuzito obugonvu (E), n’omugerageranyo gw’obuzito bw’amasavu/amasavu (F).

(G – J) Ebipimo by’obulamu bw’enkyukakyuka mu mubiri ku nkomerero y’okunoonyereza: glucose mu musaayi (G), insulini (H), ALT (I), ne triglycerides z’ekibumba (J).

(K) Okugerageranya LY3437943 ne GLP-2 ku ddoozi eyalagirwa okunoonyereza ku nkyukakyuka mu bitundu ku kikumi mu buzito bw’omubiri okumala ekiseera.

(L) Okugerageranya LY3437943 ne GLP-2 ku ddoozi eyalagirwa okunoonyereza ku kalori eziyingira mu bbanga.

Data ziragibwa nga kigero ± SEM nga n = 6 (A – L). Okwekenenya kw’ebibalo mu (C) – (K) kwakolebwa nga tukozesa ANOVA ey’engeri emu okusinziira ku mmotoka, ng’amakulu gategeezeddwa ku p < 0.05. ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001 okusinziira ku mmotoka, p < 0.05 okusinziira ku GLP-2. ALT, ekirungo kya alanine aminotransferase; LY, LY3437943, ne banne; SEM, ensobi ya mutindo gwa kigero.+

Li, Wenzhuo, n’abalala. yakozesa cryo-electron microscopy okwekenneenya GLP-3 esibiddwa ku GLP-1R, GIPR, ne GCGR. Abawandiisi baategeeza nti ekitundu kya N-terminal ekya peptide kikwatagana n’ensawo y’okusiba receptor transmembrane, ate ekitundu kya C-terminal kiyamba mu kukwatagana n’ebitundu ebikwata extracellular receptor. Okunoonyereza kuno kwazuula enkolagana zombi ezikuumibwa n’ezikwata ku bikwata mu bitundu ebisatu ebikwatagana.[3]

Joachim Neumann ne banne beekenneenya GLP-3 mu nteekateeka ez’enjawulo ez’emisuwa gya ddyo egyafunibwa nga balongoosebwa omutima. Abawandiisi baategeeza enkyukakyuka ezisinziira ku kusengejja n’obudde mu maanyi g’okukonziba era ne bakozesa ebiziyiza ebikwata ku bikwata okunoonyereza ku kwenyigira kwa GCGR, GIPR, ne GLP-1R. Bateesa ku nkola y’obubonero obukwatagana ne cAMP wansi w’embeera z’okunoonyereza kuno okwa ex vivo.[4]

Coskun ne banne. era yaloopa okunoonyereza okutali kwa bujjanjabi ku bulamu bw’emisuwa n’emisuwa mu nkimye za cynomolgus. Mu kunoonyereza okwakolebwa mu ddoozi emu, okukuba kw’omutima kwali waggulu okusinga ku bafugibwa mu kiseera kye kimu oluvannyuma lw’okukwatibwa LY3437943, nga ddoozi y’okunoonyereza ennene eyavaamu okweyongera okunene. Mu kunoonyereza okwamala emyezi mukaaga nga baddiŋŋana ddoozi, okukuba kw’omutima okwa waggulu kwalabiddwa mu kiseera ky’omutendera gw’okugaba eddagala era ne kwogerwako nga kwesigamye ku ddoozi; enkyukakyuka mu puleesa ya systolic ne diastolic nazo zaloopebwa.[2] Ebintu bino bye twetegereza byakolebwa wansi w’embeera z’okunoonyereza ku nsolo ezitali za bantu.

Ebikoma mu kunoonyereza

Ebikozesebwa mu kugezesa ebisolo biwa amawulire wansi w’embeera z’okugezesa ezitegeerekese naye tebisobola kuzaala mu bujjuvu obuzibu bw’omubiri gw’omuntu. Enjawulo mu biology y’ebikwata, okukyusakyusa mu neuroendocrine, ebbanga ly’okubikkulwa, n’obubonero obulaga wansi w’omugga biyinza okukosa okuvvuunula mu bika byonna. Ebizuuliddwa okuva mu kukebera ebikwata ku bikwata, okunoonyereza ku nsengeka, ebitundu by’omuntu ebyawuddwamu, n’ebikolwa by’ebisolo n’olwekyo birina okutaputibwa mu nkola ekozesebwa era tebirina kutwalibwa ng’obujulizi obw’obukuumi oba obulungi mu bujjanjabi.[2,4-6]

COCER Peptides egaba GLP-3 okukozesebwa mu kunoonyereza mu laboratory yokka so si kukozesebwa bantu oba ba bisolo. Ebintu ebiri ku lupapula luno bifunza ebizuuliddwa ebiwandiikiddwa mu bitabo by’abantu ab’okusatu ebijuliziddwa era tebikola bigambo bikwata ku bulung’amu bw’obujjanjabi, obukuumi, okuzuula obulwadde, obujjanjabi, okuziyiza, oba enkozesa endala ey’abantu.

▎ Ebiwandiiko Ebikwatagana

[1] KAUR M, MISRA S. Okuddamu okwetegereza eddagala erinoonyereza GLP-3, 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

[2] COSKUN T, URVA S, ROELL WC, n’abalala. LY3437943, ekipya eky’emirundi esatu glucagon, GIP, ne GLP-1 receptor agonist for glycemic control n’okugejja: Okuva ku kuzuula okutuuka ku bukakafu obw’obujjanjabi obw’endowooza[J]. Ssukaali w’obutoffaali, 2022, 34 (9): 1234-1247.e9.

DOI:10.1016/j.cmet.2022.07.013

[3] LI W, ZHOU Q, CONG Z, n’abalala. Okutegeera enzimba ku gonism ey’emirundi esatu ku GLP-1R, GIPR ne GCGR okweyolekera GLP-3[J]. Okuzuula Obutoffaali, 2024,10:77.

DOI:10.1038/s41421-024-00700-0

[4] NEUMANN J, AHLREP U, HOFMANN B, n’abalala. Ebikolwa bya inotropic ebya GLP-3 mu nteekateeka z’emisuwa gy’omuntu ezaawuddwamu[J]. Naunyn-Schmiedeberg's Archives of Eddagala, 2026,399 (1): 317-327.

DOI:10.1007/s00210-025-04421-3

[5] LUTZ T A. Ebikolwa by’ebisolo ebiyonka eby’obulwadde bwa sukaali, nga essira liteekeddwa ku ssukaali ow’ekika eky’okubiri[J]. Okuddamu okwetegereza obutonde Endocrinology, 2023,19 (6): 350-360.

DOI:10.1038/s41574-023-00818-3

[6] TU Q, LIU G, LIU X, n’abalala. Endowooza ku kukozesa ebisolo ebiyitibwa primates ebitali bantu mu kunoonyereza kwa Exposome[J]. Ecotoxicology n'obukuumi bw'obutonde, 2024,286:117199. DOI:10.1016/j.ecoenv.2024.117199.Ekitongole ky’ebyobulamu.

EBINTU BYONNNA, EBINTU, EBINTU EBY’OKUKUGU, EBINTU EBINTU EBINTU, N’AMAWULIRE ENDALA AGAWEEBWA KU MUTINDO GUNO BIGENDERERWAKO KU KUNOONYEREZA MU LABORATORI MU MATEEKA, AMAWULIRE, N’EBYENSOMESA. 

Ebintu ebiweebwa Cocer Peptides bigendereddwamu kunoonyereza mu vitro ne laboratory byokka era SSI bigendereddwamu kukozesebwa bantu oba basawo ba bisolo, kulya bantu, kukozesebwa mu bujjanjabi, okukozesebwa mu kuzuula obulwadde, okukozesebwa mu bujjanjabi, okugatta, okwegaba, okukuba empiso, oba engeri endala yonna ey’okugabira abantu oba ebisolo. Ebintu bino tebigendereddwa kuzuula, kujjanjaba, kuwonya, kukendeeza oba kuziyiza bulwadde bwonna oba mbeera ya bujjanjabi, era tebigendereddwa kukosa nsengeka oba nkola ya mubiri gwa muntu oba nsolo. Okuggyako nga kirambikiddwa bulala, ebintu ebiweebwa ku mukutu guno tebinnaba kwekenneenyezebwa oba okukkirizibwa ekitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA) okukozesebwa abantu oba abasawo b’ebisolo. Ebiwandiiko byonna ebikwata ku kunoonyereza okufulumiziddwa, amakubo g’ebiramu, enkola za molekyu, oba ebizuuliddwa mu kugezesa biweebwayo olw’okukubaganya ebirowoozo kwa ssaayansi n’okunoonyereza kwokka era tebirina magezi ga basawo, okugamba nti obujjanjabi, obulagirizi bw’okukozesa eddagala, oba ebiragiro by’okukozesa. Abaguzi be bavunaanyizibwa bokka okulaba nti ebintu byonna bifunibwa, bikwatibwa, biterekebwa, bikozesebwa, era bisuulibwa okusinziira ku mateeka agakola, ebiragiro, ebyetaago by’ebitongole, n’omutindo gw’obukuumi mu laboratory.