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1kits (Ebipipa 10) .
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▎ Enzimba ya GLP-3
Ensibuko: PubChem |
Omutendera: YA⊃1;QGTFTSDYSI-L⊃2;LDKK4AQA⊃1;AFIEYLLEGGPSSGAPPPS⊃3; Ensengekera ya molekyu: C 221H 342N 46O68 Obuzito bwa molekyu: 4731 g/mol Ennamba ya CAS: 2381089-83-2 PubChem CID: 171390338. Enkola y’okukuuma eddagala lino Ebigambo ebikwatagana:LY3437943 |
▎ Okunoonyereza ku GLP-3
GLP-3 evudde mu kunoonyereza ku ki?
Omugejjo kye kimu ku bizibu ebikulu eby’obulamu bw’abantu ennaku zino. Omugejjo guyinza okuvaako ebizibu by’obulamu eby’enjawulo, gamba ng’okukyusakyusa emmere ey’ekika eky’okubiri, endwadde z’emisuwa, puleesa, okukendeera kw’amasavu mu musaayi, n’obulwadde bw’ekibumba obw’amasavu obutali bwa mwenge. Olw’okweyongera kw’abagejjulukuka buli kiseera, waliwo obwetaavu obweyongera obw’obujjanjabi obupya obusobola okuddukanya obulungi obuzito bw’omubiri n’okutumbula embeera y’obulamu [1] . Wadde ng’okukyusakyusa mu bulamu, gamba ng’okwongera okukola emirimu gy’omubiri n’okukendeeza ku mmere gye balya, ze nkola enkulu ez’okugejja, okukuuma omugejjo okumala ebbanga eddene kikyali kusoomoozebwa eri abantu abakulu bangi abakoseddwa. GLP-3 ye agonist ey’ekipya ey’okukwata ebitundu bisatu ekola ku kirungo kya glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), ne glucagon receptor (GCGR). Enkola eno ey’okukola eya multi-receptor egiwa enkizo ez’enjawulo mu kugejja. Bw’ogeraageranya n’eddagala erikendeeza ku buzito erikola ku kifo ekimu ekikwata, 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 kugejja nnyo wabula erina n’ebizibu ebitonotono mu lubuto n’ekyenda. Okugatta ku ekyo, bw’ogeraageranya n’eddagala eddala eppya erikendeeza ku buzito, GLP-3, ng’eddagala eriziyiza okugejja emirundi esatu, erina ekikolwa eky’amaanyi ennyo eky’okugejja n’omuwendo omunene ogw’abantu abakozesebwa.
Enkola y’okukola kwa GLP-3 eri etya?
Enkola y’okukola kwa GLP-3 okusinga eva ku bikolwa byayo eby’ekika kya agonistic ku bikwata ebingi. Ekisooka, agonistic effect yaayo ku glucagon-like peptide-1 receptor (GLP-1R) eyongera ku kufulumya insulini, eziyiza okufulumya glucagon, ekendeeza ku glucose mu musaayi, ate mu kiseera kye kimu elwawo okufulumya amazzi mu lubuto, eyongera okukkuta, n’okukendeeza ku mmere [2] . Ekirala, agonistic effect yaayo ku glucose-dependent insulinotropic polypeptide receptor (GIPR) esobola okutumbula insulin secretion, okutumbula glucose utilization, era okuba n’akakwate ku masavu metabolism, okuziyiza lipolysis n’okutumbula amasavu synthesis [2] . Ekirala, newankubadde nga ekikolwa kya agonistic ekya GLP-3 ku glucagon receptor (GCGR) kitera okutumbula glycogenolysis ne gluconeogenesis mu kibumba, okwongera ku miwendo gya glucose mu musaayi, wansi w’ekikolwa kya GLP-3, ekikolwa kino eky’okwongera ku glucose mu musaayi kikyusibwakyusibwa ebikolwa by’ebikwata ebirala ebibiri. Mu kiseera kye kimu, kitumbula okusasika kw’amasavu 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 y’okulungamya emiwendo gya glucose mu musaayi, olw’okukola kwa GLP-1R ne GIPR okutumbula okufulumya insulini n’okuziyiza okufulumya glucagon, n’okukola kwa GCGR nga kukyusibwakyusibwa ebiva mu bikolwa by’ebikwata ebirala ebibiri, GLP-3 esobola bulungi okutereeza emiwendo gya glucose mu musaayi, ekintu eky’amakulu mangi mu kujjanjaba enkyukakyuka y’emmere ey’ekika eky’okubiri [1, 2] . Mu nsonga y’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu, okukola kwa GCGR kutumbula lipolysis n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu. Mu kiseera kye kimu, okukola kwa GLP-1R kwongera okukkuta n’okukendeeza ku mmere, okwongera okukendeeza ku kusengejja amasavu [1, 2] . Okugatta ku ekyo, GLP-3 era erina akakwate ak’omugaso ku bulwadde bw’ekibumba obw’amasavu obutali bwa mwenge. Kisobola okukendeeza amasavu mu kibumba n’okulongoosa enkola y’ekibumba. Okugezesebwa okwa randomized, double-blind, placebo-controlled kwalaga nti enkyukakyuka eya wakati mu masavu g’ekibumba mu kibinja eky’obujjanjabi bwa GLP-3 ku wiiki 24 yali wansi nnyo okusinga mu kibinja kya placebo [3]..
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] .
GLP-3 etereeza etya ddala enkyukakyuka ya glucose oluvannyuma lw’okukola ebikwata ku bitundu ebisatu?
GLP-3 etereeza glucose mu musaayi ng’eyita mu nkola eziwera, omuli okukola ku GLP-1 ne GIP receptors, okusitula okufulumya insulin, okuziyiza okufulumya glucagon, okulwawo okufulumya amazzi mu lubuto, okulungamya enkyukakyuka y’amasavu, n’okukendeeza ku miwendo gya ANGPTL3/8. Mu nsonga z’okulungamya glucose mu musaayi, GLP-3 ekola ku GLP-1 ne GIP receptors, okutumbula okuwuliziganya kw’obutoffaali bwa β obw’olubuto eri glucose, okusengejja n’okufulumya insulin, n’oluvannyuma okutumbula okutwalibwa n’okukozesa glucose ebitundu by’omubiri, okutuuka ku kikolwa ky’okukendeeza glucose mu musaayi [4, 5] .Mu kunoonyereza ku balwadde b’enkyukakyuka y’emmere ey’ekika eky’okubiri, . GLP-3 yalaga ekikolwa ekinene eky’okukendeeza ku glycated hemoglobin (HbA1c), ekisinga okuganyulwa mu kifo kyayo mu kusitula okufulumya insulini (Rosenstock J, 2023). Mu kiseera kye kimu, okukola ekirungo kya GLP-1 kiyinza okuziyiza okufulumya glucagon obutoffaali bwa α obw’olubuto, ne kiziyiza glucose mu musaayi okubeera waggulu ennyo. Mu kunoonyereza ku bujjanjabi, kizuuliddwa nti emiwendo gya glucagon mu balwadde abakozesa GLP-3 gikendedde, ekiyamba okukuuma obutebenkevu bwa glucose mu musaayi [4, 5] . Okukola GLP-1 ne GIP receptors nakyo kisobola okulwawo omutindo gw’okufulumya emmere mu lubuto, okukendeeza ku kugaaya n’okunyiga emmere, n’okukendeeza ku kulinnya okw’amaanyi okwa glucose mu musaayi oluvannyuma lw’okulya. Okunoonyereza kulaga nti obudde bw’okufuluma mu lubuto bw’abalwadde abajjanjabwa ne GLP-3 buwanvuwa nnyo oluvannyuma lw’okulya, bwe kityo ne kikendeeza ku muwendo gwa glucose mu musaayi ogw’oku ntikko oluvannyuma lw’okulya [4]..
Okulungamya enkyukakyuka y’amasavu nga GLP-3 nakyo kikosa enkyukakyuka ya glucose mu ngeri etali butereevu. Okugeza, mu kunoonyereza ku balwadde abagejjulukuka, kizuuliddwa nti GLP-3 esobola okukendeeza ku miwendo gya triglycerides (TG), low-density lipoprotein (LDL), ne very-low-density lipoprotein (VLDL) cholesterol [2, 6] . Okulongoosa kuno mu nkyukakyuka y’amasavu kuyinza okuba nga kwekuusa ku kulongoosa mu kuwulira kwa insulini, bwe kityo ne kiyamba mu kufuga glucose mu musaayi. Okusingira ddala, oluvannyuma lw’okujjanjabwa GLP-3, asidi wa plasma 3-hydroxybutyric (3-HB) yeeyongera, nga ewerekerwako okweyongera kwa 3-hydroxybutyrylcarnitine (C 4OH), omugerageranyo gwa acetylcarnitine ne carnitine ow’eddembe (C 2/C 0), ne acylcarnitine ow’olujegere olwa wakati, ekiraga nti lipolysis yeyongedde mu bitundu by’amasavu n’okwesigamira okweyongera ku masavu okufuuka omukka (oxidation).
GLP-3 era esobola okukendeeza ku dihydroceramides (DhCers) zonna awamu, era enkyukakyuka eno ekwatagana n’okulongoosa mu kuwulira insulini, okukendeeza ku hepatic steatosis, n’okuzimba mu nkola [6] .Mu kiseera kye kimu, GLP-3 era esobola okukendeeza ku bungi bw’ekirungo kya ANGPTL3/8 complex mu serum y’abalwadde ab’ekika kya 2 metabolism, okulungamya enkyukakyuka ya glucose [7] . ANGPTL3/8 ye ddagala erisinga okukola obulungi eriziyiza okutambula kw’omusaayi mu lipoprotein lipase (LPL), era omutindo gwayo mu musaayi gukwatagana butereevu ne TG ne low-density lipoprotein cholesterol (LDL-C). GLP-3 ekendeeza ku mutindo gwa ANGPTL3/8, eyinza okulungamya enkyukakyuka ya glucose nga ekendeeza ku lipoproteins ezirimu triglyceride [7]. .
Mu nsonga ki GLP-3 gy’eraga ebikolwa byayo?
Ekikulu ekiva mu kugejja:
GLP-3 eraga ebikolwa eby’amaanyi mu kugejja mu kugezesebwa okw’obujjanjabi okungi. Okugeza, mu kunoonyereza okwakolebwa mu bujjanjabi okwali kuzingiramu abantu abakulu 338 [2] , abalwadde abajjanjabwa ne dose ez’enjawulo eza GLP-3 baalina okugejja okw’amaanyi ku wiiki 48. Mu bano, abalwadde mu kibinja kya dose ya 12mg baalina okugejja kwa 24.2%, 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 baakendeeza ku buzito bw’omubiri gwabwe ebitundu 5% oba okusingawo. Mu kunoonyereza okulala [8] , okugezesebwa okubiri okufugibwa okwakolebwa mu ngeri ey’ekifuulannenge okwali kuzingiramu abalwadde 353 abakola ku nkyukakyuka y’emmere ey’ekika kya 2 kwalaga nti bw’ogeraageranya n’eddagala erya placebo, GLP-3 esobola okukendeeza ennyo ku buzito bw’omubiri gw’abalwadde ne kkiro 11.89 n’okukendeeza ku glycated hemoglobin (HbA1C). Okugatta ku ekyo, mu kugezesebwa okwakolebwa ku balwadde abakulu abagejjulukuka abatali ba ssukaali, 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'enkyukakyuka y'emmere ey'ekika kya 2 :
GLP-3 era eraga obusobozi obumu mu kujjanjaba enkyukakyuka y’emmere ey’ekika eky’okubiri. Mu kugezesebwa okumu, GLP-3 eraga okukendeera mu glycated hemoglobin (HbA1c) n’okugejja okusinziira ku ddoozi. Okugeza, mu kunoonyereza okumu, mu balwadde b’ekika kya 2 metabolism, GLP-3 yalaga ekikolwa ekinene eky’okufuga glucose mu musaayi, okukendeeza ku glycated hemoglobin ne 1.64% bw’ogeraageranya ne placebo [4, 8] . 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 byalaga okukendeera okw’amaanyi mu glycated hemoglobin levels n’okugejja okusinziira ku dose oluvannyuma lw’okufuna obujjanjabi bwa GLP-3 [4] . Kino kiyinza okuva ku bikolwa byonna eby’eddagala lino ku GLP-1, GCGR, ne GIPR, ebirongoosa enkyukakyuka ya glucose n’okutebenkeza amaanyi.
Okulongoosa mu bintu ebiyinza okuleeta akabi ku misuwa gy’omutima:
GLP-3 tesobola kukendeeza ku buzito bw’omubiri gwokka wabula n’okulongoosa ebintu ebiyinza okuleeta akabi ku misuwa gy’omutima, 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 b’enkyukakyuka mu mubiri, bwe kityo ne kikendeeza ku bulabe bw’ebizibu by’emisuwa gy’omutima [8-10]. .
Obujjanjabi bw’obulwadde bw’ekibumba obutaliimu masavu (NAFLD):
GLP-3 ye peptide empya eya triple receptor agonist peptide 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 mu kujjanjaba obulwadde bw’ekibumba obw’amasavu obutali bwa mwenge. Mu kunoonyereza okumu, okugezesebwa okwa randomized, double-blind, placebo-controlled trial okwamala wiiki 48 kwakolebwa 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 okusinziira 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%, ate nga ezo mu kibinja kya placebo zaali +0.3% [3] . 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. Kiyinza okukola ekirungo kya glucagon, ekikwata insulinotropic polypeptide eyeesigama ku glucose, n’ekirungo kya glucagon-like peptide-1, okulungamya mu bujjuvu enkyukakyuka y’omubiri okuva mu bipimo ebingi, okulongoosa okufuga glucose mu musaayi, okukendeeza ku buzito bw’omubiri, n’okulungamya enkyukakyuka y’amasavu. Okujja kwa GLP-3 kuleeta enkola empya ez’obujjanjabi eri abalwadde abagejjulukuka, enkyukakyuka y’omubiri ey’ekika eky’okubiri, n’endwadde endala. Kisuubirwa okumenyawo obuzibu bw’eddagala ly’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 nabyo, okutumbula omutindo gw’obulamu bw’abalwadde, n’okukendeeza ku buzito bw’obujjanjabi mu mbeera z’abantu.
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].
