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1kits (Ebipipa 10) .
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▎ Okunoonyereza ku GLP-3
GLP-3 evudde mu kunoonyereza ku ki?
Omugejjo gufuuse ekimu ku bisinga okusoomoozebwa mu bulamu bw’abantu mu bantu ab’omulembe guno. Kiyinza okuvaako ebizibu by’obulamu bingi nga type 2 metabolism mellitus, endwadde z’emisuwa, puleesa, dyslipidemia, n’obulwadde bw’ekibumba obutaliimu mwenge. Olw’okweyongera kw’abagejjulukuka buli kiseera, waliwo obwetaavu obweyongera obw’amangu obw’obujjanjabi obupya obusobola okuddukanya obulungi obuzito bw’omubiri n’okulongoosa embeera z’obulamu [1] . Newankubadde nga okuyingira mu bulamu, gamba ng‟okwongera okukola emirimu gy‟omubiri n‟okufuga emmere, bye bipimo ebikulu eby‟okuziyiza omugejjo, kizibu nnyo eri abalwadde bangi abakulu abagejjulukuka okukuuma okugejja okumala ebbanga eddene.
GLP-3, nga ekirungo ekipya ekiziyiza okukwata ebitundu bisatu, asobola okukola ku kirungo ekikwata peptide-1 ekiringa glucagon (
GLP-1R), ekirungo kya insulinotropic polypeptide ekisinziira ku glucose (GIPR), n’ekirungo kya glucagon (GCGR). Enkola eno ey’okukola eya multi-receptor egiwa enkizo ennene mu kisaawe ky’okugejja. Bw’ogeraageranya n’eddagala erikendeeza ku buzito erikola ku kifo kimu kyokka, GLP-3 esobola okulung’amya mu bujjuvu enkola z’omubiri ez’okukyusakyusa ebiriisa [1] . GLP-3 etuuka ku kugejja ng’etereeza ebifo ebikwata obusimu ebingi, tekoma ku kulaga bulungibwansi bwa kitalo naye era n’ebizibu ebitonotono mu lubuto n’ekyenda. Okugatta ku ekyo, nga triple receptor agonist, GLP-3 erina amaanyi amangi agakola ku kugejja n’omuwendo omunene ogw’abantu abakozesebwa bw’ogeraageranya n’eddagala eddala eppya erigejja.
GLP-3 kye ki?
GLP-3 ye nkola empya ekola okumala ebbanga eddene nga glucagon-like peptide-1 (GLP-1) receptor agonist. Kikyusibwa era ne kirongooseddwa okusinziira ku nsengeka ya GLP-1 ey’obutonde, era kisobola okwesiba mu ngeri ey’enjawulo n’okukola ku GLP-1 receptor, okukola emirimu gy’omubiri egy’obutonde okufaananako n’egya GLP-1 ey’obutonde, gamba ng’okutumbula okufulumya insulini, okuziyiza okufulumya glucagon, okulwawo okufulumya amazzi mu lubuto, okukendeeza ku njagala y’okulya, n’ebirala Kirina essuubi ery’okukozesebwa mu bugazi mu kujjanjaba enkyukakyuka mu mubiri n’okuddukanya obuzito.
Enkola y’okukola kwa GLP-3 eri etya?
Enkola y’okukola kwa GLP-3 eva ku bikolwa byayo eby’okuziyiza (agonistic effects) ku bikwata ebingi. Ekisooka, agonistic effect yaayo ku glucagon-like peptide-1 receptor (GLP-1R) esobola okwongera ku kufulumya insulini, okuziyiza okufulumya glucagon, okukendeeza ku glucose mu musaayi, ate mu kiseera kye kimu okulwawo okufulumya amazzi mu lubuto, okwongera okukkuta, n’okukendeeza ku mmere gy’olya [2] . Ekirala, agonistic effect yaayo ku glucose-dependent insulinotropic polypeptide receptor (GIPR) esobola okutumbula okufulumya insulin, okutumbula enkozesa ya glucose, n’okukosa metabolism y’amasavu, okuziyiza lipolysis n’okutumbula okukola amasavu [2] . Ekirala, agonistic effect ya GLP-3 ku glucagon receptor (GCGR) etera okutumbula glycogenolysis ne gluconeogenesis mu kibumba, okwongera ku glucose mu musaayi. Naye, wansi w’ekikolwa kya GLP-3, kino ekikolwa eky’okusitula glucose kikyusibwakyusibwa ebikolwa by’ebikwata ebirala ebibiri, ate nga kitumbula lipolysis n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu [2] . Enkola eno ey’okukola erimu ebigendererwa ebingi eyinza okuba ennungi mu kujjanjaba omugejjo okusinga eddagala eriziyiza obuwuka obuyitibwa single receptor agonists.
Nga ekola mu kiseera kye kimu ebikwata bino ebisatu, GLP-3 esobola okukola ebikolwa eby’enjawulo ebifuga enkyukakyuka mu mubiri n’okufulumya ebikolwa eby’obujjanjabi ku mugejjo n’endwadde ezikwatagana nabyo. Mu nsonga z’okulungamya emiwendo gya glucose mu musaayi, okuva okukola kwa GLP-1R ne GIPR bwe kutumbula okufulumya insulini n’okuziyiza okufulumya glucagon, era okukola kwa GCGR kukyusibwakyusibwa ebiva mu bikolwa by’ebikwata ebirala ebibiri, GLP-3 esobola bulungi okutereeza emiwendo gya glucose mu musaayi, ekintu eky’amakulu mangi mu kujjanjaba ekika kya 2 metabolism mellitus [1, 2] . Mu nsonga y’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu, okukola kwa GCGR kutumbula lipolysis n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu, ate okukola kwa GLP-1R kwongera okukkuta n’okukendeeza ku mmere, okwongera okukendeeza ku kusengejja amasavu [1] . Okugatta ku ekyo, GLP-3 era erina ekikolwa ekirongoosa ku bulwadde bw’ekibumba obw’amasavu obutali bwa mwenge. Kisobola okukendeeza amasavu mu kibumba n’okulongoosa enkola y’ekibumba.
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] .
Mu nsonga ki GLP-3 gy’eraga ebikolwa byayo?
GLP-3 eraga ebikosa ebinene mu bintu ebingi
Ekinene ekiva mu kugejja: GLP-3 eraga ebikolwa ebinene mu kugejja mu kugezesebwa okw’obujjanjabi okungi. Okugeza, mu kunoonyereza okwakolebwa mu bujjanjabi okwali kuzingiramu abantu abakulu 338 (Jastreboff AMM, 2023), abalwadde abajjanjabwa ne dose ez’enjawulo eza GLP-3 baafuna okugejja okw’amaanyi ku wiiki 48. Mu bano, abalwadde mu kibinja kya ddoozi ya 12mg baafiirwa ebitundu 24.2% ku buzito bw’omubiri gwabwe, era ekitundu ekinene eky’abalwadde baatuuka ku kugejja ku diguli ez’enjawulo. Okugeza, mu balwadde abafuna dose ya 4mg, 8mg, ne 12mg, 92%, 100%, ne 100% ku balwadde, okusinziira ku, baakendeeza ku buzito bw’omubiri gwabwe ebitundu 5% oba okusingawo. Mu kunoonyereza okulala [3] , okugezesebwa okubiri okufugibwa okutali kwa bulijjo okwazingiramu abalwadde 353 abalina ekika kya 2 metabolism mellitus kwalaga nti bw’ogeraageranya ne placebo, GLP-3 esobola okukendeeza ennyo ku buzito bw’omubiri gw’abalwadde ne 11.89kg, era n’okukendeeza ku glycated hemoglobin (HbA1C). Okugatta ku ekyo, mu kugezesebwa kw’abalwadde abakulu abagejjulukuka nga tebalina nkyukakyuka mu mubiri, GLP-3 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 GLP-3 erina obusobozi bungi mu kugejja.
Obujjanjabi bw’ekika kya 2 metabolism mellitus: GLP-3 era eraga obusobozi obumu mu kujjanjaba ekika kya 2 metabolism mellitus. Mu kugezesebwa okumu, GLP-3 eraga okukendeera mu glycated hemoglobin (HbA1c) n’okugejja okusinziira ku ddoozi. Okugeza, mu kunoonyereza okumu, mu balwadde abalina ekika kya 2 metabolism mellitus, GLP-3 yalaga ebikolwa ebinene eby’okufuga glucose mu musaayi. Bw’ogeraageranya n’eddagala erya placebo, glycated hemoglobin yakendeera ebitundu 1.64% [3] . 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 mellitus, oluvannyuma lw’okufuna obujjanjabi bwa GLP-3, byalaga okukendeera okw’amaanyi mu glycated hemoglobin levels, era obuzito bw’omubiri gwabwe nagwo bwakendeera mu ngeri eyeesigama ku dose [4] . Kino kiyinza okuva ku bikolwa byonna eby’eddagala lino ku GLP-1, GCGR, ne GIPR, ebirongoosa enkyukakyuka ya glucose n’okutebenkeza amaanyi.
Okulongoosa ensonga z’obulabe eri emisuwa: GLP-3 tesobola kukendeeza ku buzito bw’omubiri bwokka 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 GLP-3 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 abalina enkyukakyuka mu mubiri, bwe kityo ne kikendeeza ku bulabe bw’ebizibu by’emisuwa [3, 5, 6]..
Obujjanjabi bw’obulwadde bw’ekibumba obw’amasavu obutali bwa mwenge (NAFLD): GLP-3 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 GLP-3 erina obusobozi okujjanjaba obulwadde bw’ekibumba obw’amasavu obutali bwa mwenge. Mu kunoonyereza okumu, okugezesebwa okwa randomized, double-blind, placebo-controlled trial kwakolebwa okumala wiiki 48 ku beetabye mu kunoonyereza kuno 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 okuva ku ntandikwa mu beetabye mu kujjanjabwa ne dose ez’enjawulo eza GLP-3 (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% [7] . Kino kiraga nti GLP-3 eyinza okuba n’akakwate akakulu mu bujjanjabi ku bulwadde bw’ekibumba obw’amasavu obutali bwa mwenge.
Mu kumaliriza, nga novel triple receptor agonist, GLP-3 eraga obusobozi bungi mu kujjanjaba omugejjo n’endwadde ezikwatagana nabyo. Kisobola okutereeza enkyukakyuka y’omubiri gw’omuntu okuva mu bipimo ebingi nga kikola ekirungo kya glucagon, ekikwata insulinotropic polypeptide eyeesigama ku glucose, n’ekirungo kya peptide-1 ekiringa glucagon, okulongoosa okufuga glucose mu musaayi, okukendeeza ku buzito bw’omubiri, n’okutereeza enkyukakyuka y’amasavu. Okujja kwa GLP-3 kuleese enkola empya ez’obujjanjabi eri abalwadde abagejjulukuka, ekika kya 2 metabolism mellitus, n’ebirala 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, okutumbula omutindo gw’obulamu bw’abalwadde, n’okukendeeza ku bujjanjabi bw’embeera z’abantu omugugu.
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].
