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.
Ennyonyola ya AOD9604
AOD9604 ye peptide eggibwa mu kitundu kya C-terminal fragment of human growth hormone (hGH). Kirimu amino asidi 177–191 eza hGH, nga waliwo ekisigadde kya tyrosine ekirala (Tyr) ekigattibwa ku nkomerero ya N-terminal eya peptide, kwe kugamba, Tyr-hGH 177–191. Omutendera gwa amino asidi ogwa AOD9604 gwe gusalawo ensengekera yaayo ey’ekifo, nga kino nakyo kikwata ku nkolagana yaayo n’ebikwata ne molekyu ez’enjawulo mu mubiri. Ebisigadde bya tyrosine ebigattibwa ku N-terminus biyinza okukosa okutebenkera kwa peptide mu mubiri, obulungi bw’okutwala obutoffaali, n’enkolagana y’okusiba n’ebikwata ebitongole. AOD9604 eri mu kibinja ky’ebirungo bya peptide, ebyetaba mu nkola ez’enjawulo ez’omubiri mu mubiri, gamba ng’okukyusa obubonero n’okulungamya enkyukakyuka mu mubiri. Olw’ensibuko yaayo entongole n’ensengeka yaayo, AOD9604 erina emirimu egy’enjawulo egy’omubiri, naddala ng’eraga ebikolwa ebinene mu kulungamya enkyukakyuka y’amasavu.
Enkola ya AOD9604 mu kulungamya Enkyukakyuka y’amasavu
(1) Okukwatagana n’ekkubo lya β-adrenergic
Okulungamya okwolesebwa kw’ekirungo kya β-adrenergic: AOD9604 eyinza okukwata ku nkyukakyuka y’amasavu ng’ekwatagana n’ekkubo lya β-adrenergic, naddala okuyita mu kulungamya β (3)-adrenergic receptor (β (3)-AR). Mu model y’ebibe omugejjo, oluvannyuma lw’ennaku 14 ez’omuddiring’anwa ez’empiso ya AOD9604 mu lubuto, omutindo gw’okwolesebwa kwa β (3)-AR RNA mu adipocytes gweyongera. β(3)-AR ye lipolytic receptor enkulu mu adipocytes, era okweyongera kwayo okwolesebwa kutumbula lipolysis. AOD9604 eyinza okutumbula okwolesebwa kw’obuzaale bwa β(3)-AR nga ekola amakubo g’obubonero agakwatagana, bwe kityo n’eyongera ku kwolesebwa kwayo okw’okungulu mu butoffaali. Kiyinza okukwata ku kusiba kw’ensonga ezimu ez’okuwandiika ku kitundu kya promoter eky’obuzaale bwa β(3)-AR, bwe kityo ne kyongera ku bulungibwansi bw’okutandika okuwandiika obuzaale.
Enkola za cascading ez’okukola ekkubo lya β-adrenergic: Okwolesebwa kwa β (3)-AR bwe kweyongera, kwesiba ku ligandi okukola amakubo g’obubonero aga wansi. β(3)-AR ekola ekwatagana ne puloteyina za G, ekivaako okukola kwa adenylate cyclase, nga kino nakyo kyongera ku miwendo egy’omu butoffaali egy’omubaka owookubiri cyclic adenosine monophosphate (cAMP). cAMP ekola protein kinase A (PKA), ekola phosphorylate n’okukola hormone-sensitive lipase (HSL), enzyme enkulu mu lipolysis ekola ku hydrolysis ya triglycerides mu fatty acids ne glycerol, bwe kityo ne kitumbula lipolysis n’okulungamya lipid metabolism.
(2) Ebikosa obutereevu ebitali bya β(3)-AR
Ebizuuliddwa mu kugezesa okw’amangu: Mu kugezesa okw’amangu ku mbeba ezikoona obuzaale bwa β(3)-AR, AOD9604 ekyayongera ku nsaasaanya y’amaanyi n’okuziyiza amasavu. Kino kiraga nti AOD9604’s regulatory effect ku lipid metabolism tesinziira ddala ku β(3)-AR. Newankubadde enkola entongole tennategeerekeka bulungi, amakubo amalala oba ebigendererwa by’okukola obutereevu biyinza okubaawo. AOD9604 eyinza okukola butereevu ku mitochondria, okukwata ku nkola ya mitochondria n’okutumbula β-oxidation ya fatty acids. Mitochondria ze bifo eby’omu makkati eby’okukyusakyusa amaanyi g’obutoffaali, era fatty acid β-oxidation ebaawo mu mitochondria. AOD9604 esobola okutumbula okuyingira kwa asidi w’amasavu mu mitochondria n’okwanguyiza okuvunda kw’okwokya (oxidative degradation) ng’etereeza emirimu gya puloteyina ezitambuza oba enziyiza ezikwatagana ku luwuzi lwa mitochondria, bwe kityo n’eyongera ku nsaasaanya y’amasoboza n’okuwunyiriza kwa asidi w’amasavu.
Amakubo amalala agayinza okuweebwa obubonero: AOD9604 era yeenyigira mu kulungamya amakubo amalala agalaga obubonero. Kiyinza okukwata ku mirimu gy’amaka ga peroxisome proliferator-activated receptor (PPAR). PPARs kibiina kya nuclear receptors ezikola omulimu omukulu ogw’okulungamya mu nkyukakyuka y’amasavu, bbalansi y’amasoboza, n’okuddamu kw’okuzimba. AOD9604 esobola okukwatagana ne PPARs okulungamya okwolesebwa kw’obuzaale bwazo obugendererwa, bwe kityo n’ekosa okuwandiika n’okuvvuunula obuzaale obukwatagana n’enkyukakyuka y’amasavu, bwe kityo n’etereeza enkyukakyuka y’amasavu. Era kiyinza okwetaba mu kulungamya ekkubo ly’obubonero bwa insulini. Wadde nga AOD9604 terina bikolwa bibi ebireeta ssukaali ebikwatagana ne hGH, eyinza okukwata mu ngeri etali butereevu enkola z’okukyusakyusa amasavu ng’etereeza obulungi ekkubo ly’obubonero bwa insulini.
Ebiva mu AOD9604
(1) Ebikosa obuzito bw’omubiri n’amasavu
Obujulizi obw’okugezesa ebisolo: Mu nkola y’ekibe ekinene ennyo, okukuba empiso ya AOD9604 mu lubuto okumala ebbanga eddene (ennaku 14 ez’okugiwa okumala ebbanga eddene) yakendeeza nnyo ku buzito bw’omubiri n’amasavu mu mubiri. Okukendeera kuno mu buzito bw’omubiri n’amasavu kwakwatagana n’okweyongera kw’emiwendo gy’okwolesebwa kwa β(3)-AR RNA, ekiraga nti AOD9604 etumbula lipolysis ng’etereeza β(3)-AR expression, bwe kityo ne kituuka ku kukendeera mu buzito bw’omubiri n’amasavu mu mubiri. Okusingira ddala, waaliwo okukendeera mu buzito bw’amasavu agali wansi w’olususu n’ag’omu bitundu by’omubiri, awamu n’okugejja okutwalira awamu. Mu kugezesa, okupima obuzito bw’ebibe buli kiseera n’okupima okutuufu okw’obuzito bw’ebitundu by’amasavu oluvannyuma lw’okufa kwalaga nti ebibe ebyajjanjabwa AOD9604 byalaga okukendeera ennyo ku buzito bw’omubiri n’obuzito bw’amasavu bw’ogeraageranya n’ekibinja ekifuga, ng’okukendeera kuno kulaga omuze ogwesigamye ku ddoozi.
Ekifaananyi 2 Ebigendererwa by’eddagala mu kiseera kino n’eby’omu maaso mu kuddukanya obuzito
Ku bujjanjabi bw’omugejjo gw’abantu, ebiva mu AOD9604 bikwata omugaso oguyinza okukozesebwa. Omugejjo nsonga nkulu mu bulabe eri endwadde nnyingi ezitawona ng’endwadde z’emisuwa n’emisuwa ne ssukaali, era okukendeeza ku buzito bw’omubiri n’amasavu kikulu nnyo mu kulongoosa embeera y’obulamu bw’abalwadde abagejjulukuka.
(2) Ebikosa Enkyukakyuka y’Amaaso
Okwongera ku nsaasaanya y’amasoboza: AOD9604 eyongera ku nsaasaanya y’amasoboza mu mbeba zombi eza bulijjo n’embeba ezikoona obuzaale bwa β(3)-AR. Mu mbeba eza bulijjo, indirect calorimetry yakozesebwa okupima enkozesa ya oxygen n’okukola carbon dioxide, ne kizuula nti AOD9604 yayongera nnyo ku miwendo gy’okukyusakyusa amaanyi. Ekikolwa kino kiva ku AOD9604 okutumbula lipolysis, nga asidi z’amasavu ezifulumizibwa zikola nga substrates z’amasoboza okukola oxidation n’okukozesa, bwe kityo ne kyongera ku nsaasaanya y’amasoboza. Mu mbeba β (3)-AR knockout, wadde ng’enkola yaayo ey’okukola tesinziira ku β (3)-AR, okweyongera mu nsaasaanya y’amasoboza kwakyalabiddwa, ekyongera okulaga nti AOD9604 erina ekkubo ly’okulungamya enkyukakyuka y’amasoboza eyeetongodde ku β (3)-AR.
Okulungamya okuzimba amasavu: AOD9604 eyongera ku nkola y’okuziyiza amasavu. Mu kugezesa kw’obutoffaali, nga tukozesa asidi z’amasavu eziwandiikiddwa mu ngeri ya radioactively okulondoola enkyukakyuka yazo ey’okwokya, kyazuulibwa nti omutindo gw’okuwunyiriza kwa asidi z’amasavu gwayanguyirwa mu butoffaali obujjanjabiddwa ne AOD9604. Kino tekikoma ku kuyamba kukendeeza kutereka masavu wabula n’okuwa omubiri amaanyi amangi. AOD9604 eyinza okutumbula obulungi bwa fatty acid oxidation efficiency nga etereeza enkola ya mitochondrial, okwongera ku mitochondrial biogenesis n’emirimu. Kitumbula okwolesebwa n’emirimu gy’enziyiza ezikwatagana n’okuwunyiriza asidi z’amasavu mu mitochondria, omuli carnitine palmitoyltransferase I (CPT-I), nga eno ye enzyme enkulu ekoma ku mutindo gwa asidi z’amasavu eziyingira mu mitochondria okukola oxidation. AOD9604 eyinza okutumbula okuyingira kwa asidi w’amasavu mu mitochondria okusobola okuvunda mu oxidative nga upregulating CPT-I expression.
(3) Ebikosa enkyukakyuka y’amasavu mu kibumba
Okunoonyereza ku kugezesa ebisolo ku nkyukakyuka y’amasavu mu kibumba: Mu nkola y’ekibumba ky’amasavu mu mbeba, ebikolwa bya AOD9604 ku nkyukakyuka y’amasavu mu kibumba byanoonyezebwa. Ebibe byagabanyizibwamu ekibinja ekifuga, ekibinja eky’okukola dduyiro, ekibinja eky’okukola dduyiro + AOD9604, n’ekibinja eky’obujjanjabi bwa AOD9604 yokka. Ebivuddemu biraga nti emiwendo gya alanine aminotransferase (ALT) mu kibinja kya AOD9604 yokka n’ekibinja kya exercise + AOD9604 gyali wansi nnyo okusinga egyo mu kibinja ekifuga, ekiraga nti AOD9604 erina ekikolwa ekimu eky’obukuumi ku kwonooneka kw’ekibumba. Kino kiyinza okuva ku AOD9604 okulungamya enkyukakyuka y’amasavu mu kibumba, okukendeeza ku kukuŋŋaanyizibwa kw’amasavu mu kibumba, bwe kityo ne kikendeeza ku kuzimba kw’ekibumba n’okuddamu kw’okuzimba.
Ebikosa enziyiza z’ekibumba ne cytokeratin-18 (CK18): Cytokeratin-18 ye biomarker eraga hepatocyte apoptosis. Mu kugezesa, wadde ng’ekibinja ky’obujjanjabi obw’ekimu ekya AOD9604 tekyakendeeza nnyo ku miwendo gya CK18, era tekyavaamu bikolwa bibi. Kino kiraga nti AOD9604 eyinza okukwata mu ngeri etali butereevu enkola y’okufa kw’obutoffaali bw’ekibumba ng’etereeza enkyukakyuka y’amasavu mu kibumba, bwe kityo n’ekuuma obutoffaali bw’ekibumba obutakwonooneka okutuuka ku ddaala eritali limu. AOD9604 eyinza okukuuma bbalansi y’okukyusakyusa amasavu mu kibumba ng’etereeza okwolesebwa kw’obuzaale obukwatagana n’okusengejja amasavu, okutambuza, n’okuvunda mu kibumba, bwe kityo n’ekendeeza ku kukuŋŋaanyizibwa kw’amasavu mu ngeri etaali ya bulijjo mu kibumba.
Okukozesa kwa AOD9604
(1) Ebiyinza Okukozesebwa mu Bujjanjabi bw’Omugejjo
Ebirungi n’ebisuubirwa: Bw’ogeraageranya n’eddagala ery’ekinnansi erikendeeza ku mugejjo, AOD9604 erina ebirungi ebiwerako ebiyinza okuvaamu. Tekirina bizibu ebiva ku ssukaali ebikwatagana ne hGH. hGH eyinza okuleeta ebizibu nga obutaziyiza insulini n’okulinnya kwa glucose mu musaayi bw’ekozesebwa okujjanjaba omugejjo. AOD9604 yeewala ebizibu bino ng’eyita mu nteekateeka yaayo ey’enjawulo ey’enzimba. AOD9604 esobola okulung’amya mu ngeri ey’enjawulo enkyukakyuka y’amasavu, okutumbula okumenya amasavu, n’okwongera ku nsaasaanya y’amaanyi, n’ewa essuubi ly’obujjanjabi erisuubiza eri abalwadde abalina omugejjo omutono. Enkola yaayo ey’okukola erimu emitendera mingi, si okuyita mu kulungamya ekkubo lya β-adrenergic lyokka wabula n’okuyita mu nkola eyetongodde ku β(3)-AR, egaba enkola ey’okuyingira mu nsonga esingawo enzijuvu ku bujjanjabi bw’omugejjo.
(2) Ebiyinza okukozesebwa mu kujjanjaba endwadde z’ekibumba
Obusobozi bw’okujjanjaba obulwadde bw’ekibumba obutali bwa mwenge (NAFLD): NAFLD bulwadde bwa kibumba obwa bulijjo obumanyiddwa ng’amasavu agasukkiridde okukuŋŋaanyizibwa mu kibumba. Mu model y’ebibe ey’obulwadde bw’ekibumba obw’amasavu, AOD9604 esobola okulungamya enkyukakyuka y’amasavu mu kibumba, okukendeeza ku masavu mu kibumba, n’okulongoosa obubonero bw’enkola y’ekibumba. AOD9604 erina omuwendo ogugere ogw’okukozesa mu kujjanjaba NAFLD. Kiyinza okukendeeza ku kukuŋŋaanyizibwa kw’amasavu mu kibumba nga kitumbula okumenya n’okutambuza amasavu munda mu kibumba, bwe kityo ne kikendeeza ku kuzimba kw’ekibumba n’okuddamu kw’okuzimba. AOD9604 era esobola okulungamya oxidative stress ne inflammatory signaling pathways munda mu kibumba, okwongera okukuuma obutoffaali bw’ekibumba obutakwonooneka.
Mu bufunzi
Nga peptide evudde mu kitundu kya C-terminal eky’obusimu bw’okukula kw’omuntu, enkola ya AOD9604 ey’okukola mu kulungamya enkyukakyuka y’amasavu erimu enkolagana n’ekkubo lya β-adrenergic n’ebikolwa obutereevu ebitali bya β (3)-AR. Okuyita mu nkola zino, AOD9604 ekendeeza bulungi ku buzito bw’omubiri n’amasavu mu mubiri, eyongera ku nsaasaanya y’amaanyi, etereeza oxidation y’amasavu, n’okulongoosa enkyukakyuka y’amasavu mu kibumba. Mu ngeri y’okukozesaamu, AOD9604 esuubiza nnyo mu kujjanjaba omugejjo, eddagala ly’emizannyo, n’endwadde z’ekibumba.
Ensonda
[1] Dehbashi M, Fathi M, Attarzadeh Hosseini S. R., n’abalala. Enkola y’okutendekebwa mu kugumiikiriza okwa wiiki munaana, empiso ya Somatropin, n’ekitundu kyayo eky’amasavu (AOD9604) ku Cytokeratin-18 ne Enzymes z’ekibumba ez’ebibe ebireetebwa okwonooneka kw’ekibumba olw’emmere erimu amasavu amangi[J]. Quarterly of the Horizon ya Sayansi w’Ebyobujjanjabi, 2021,27:502-517.DOI:10.32598/hms.27.4.3513.1.
[2] Cox HD, Smeal SJ, Hughes C. M., n’abalala. Okuzuula n’okukyusakyusa mu mubiri (in vitro metabolism) kwa AOD9604[J]. Okukebera n'okwekenneenya eddagala, 2015,7 (1): 31-38.DOI: 10.1002 / dta.1715.
[3] Stier H, Vos E, Kenley D L. Obukuumi n’okugumiikiriza kwa Hexadecapeptide AOD9604 mu Bantu[J]. Journal of Endocrinology n'enkyukakyuka mu mubiri, 2013,3:7-15.
https://api.semanticscholar.org/CorpusID:56559133. Enkola y’okukuuma obutonde bw’ensi
[4] Witkamp R F. Ebigendererwa by’eddagala mu kiseera kino n’eby’omu maaso mu kuddukanya obuzito[J]. Okunoonyereza ku ddagala, 2011, 28 (8): 1792-1818.DOI: 10.1007 / s11095-010-0341-1.
Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
