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.
Growth Hormone (GH) ekola kinene nnyo mu nkola nnyingi ez’omubiri, omuli okukula, enkula, n’okulungamya enkyukakyuka mu biramu. Okufuluma kwayo kulung’amibwa bulungi enkola y’obusimu enzibu, era Growth Hormone-Releasing Peptides (GHRPs) kibiina kya bintu ebisitula okufulumya obusimu bw’okukula, ekisikiriza okufaayo okunene okuva mu banoonyereza. Ipamorelin, nga mmemba mu famire ya GHRP, ya njawulo olw’ensengeka yaayo ey’enjawulo n’obusobozi bwayo obw’amaanyi okutumbula okufulumya obusimu bw’okukula.
Okusinziira ku ndowooza y’ensengekera y’eddagala, Ipamorelin ye pentapeptide ekoleddwa. Ensengekera eno egiwa enkolagana ey’amaanyi eri Growth Hormone-Releasing Peptide Receptor (GHRP-R), ekigisobozesa okukola obulungi ekikwata n’okutandikawo amakubo agawerako ag’obubonero mu butoffaali, bwe kityo ne kitumbula okufulumya obusimu obukula.
Bw’ogeraageranya n’obusimu obufulumya obusimu bw’okukula (GHRH), Ipamorelin erimu ebirungi eby’enjawulo ebiwerako. GHRH okusinga ekola ku bikwata GHRH ku ngulu w’obutoffaali bw’obusimu obukula mu nseke y’omu maaso okusitula okusengejja n’okufulumya obusimu bw’okukula. Ipamorelin tekoma ku kukola butereevu ku nseke ya pituitary wabula era mu ngeri etali butereevu etereeza okufulumya obusimu bw’okukula ng’ekola ku hypothalamus n’ebitundu ebirala, n’ewa amakubo ag’enjawulo ag’ebikolwa. Ipamorelin eraga okulonda okw’amaanyi mu kutumbula okufulumya obusimu bw’okukula, eraga ekikolwa eky’okusitula ennyo ku kufulumya obusimu bw’okukula ate ng’erina akakwate katono ku miwendo gya plasma egy’obusimu obulala obw’omu nseke nga obusimu obusitula enkwaso (FSH), obusimu obukola luteinizing (LH), prolactin (PRL), n’obusimu obusitula thyroid (TSH).
Mu kugezesa ebisolo, Ipamorelin yalaga obulungi ennyo mu kutumbula okufulumya obusimu bw’okukula mu bika by’ebisolo eby’enjawulo, omuli envunza, embizzi, endiga, n’embwa. Mu kugezesa envunza, oluvannyuma lw’okuweebwa Ipamorelin, okweyongera okw’amangu mu miwendo gy’obusimu obukula mu plasma kwalabiddwa, nga kulaga enkolagana eyesigamiziddwa ku ddoozi. Kino kiraga nti Ipamorelin esobola bulungi okulung’amya okufulumya obusimu bw’okukula, n’awa obujulizi obw’okugezesa obw’amaanyi ku ngeri gy’eyinza okukozesebwamu mu kulongoosa enkola y’okukula kw’ebisolo n’okujjanjaba endwadde ezikwatagana nabyo.
Ekifaananyi 1 Omulongooti 1 Enkolagana y’enzimba–emirimu gy’ebimu ku pentapeptides empya ku GH okufuluma okuva mu butoffaali bw’envunza mu vitro – okugeraageranya ne GHRP-1, GHRP-2, GHRP-6, ne GHRH. Ebivuddemu biragiddwa nga kitegeeza ± SEM (n = 3–6 okugezesa okw’enjawulo).
Enkola y’okukola kwa Ipamorelin mu kutumbula okufulumya obusimu bw’okukula
Enkolagana n’ekirungo kya peptide ekifulumya obusimu bw’okukula
Omutendera omukulu ogusooka mu mulimu gwa Ipamorelin mu kutumbula okufulumya obusimu bw’okukula kwe kusiba kwayo okwetongodde ku peptide receptor efulumya obusimu bw’okukula (GHRP-R). GHRP-R eri mu G protein-coupled receptor superfamily era esaasaanidde nnyo mu anterior pituitary, hypothalamus, n’ebitundu ebirala eby’okumpi. Ensengekera ya pentapeptide eya Ipamorelin egisobozesa okukwatagana obulungi n’ensawo ekwata ligandi eya GHRP-R, ekivaako enkyukakyuka mu nsengekera mu kisengejja. Enkyukakyuka eno ey'ensengekera ekola nga 'switch' okutandika okukyusa obubonero mu butoffaali, okusobozesa GHRP-R okukwatagana n'okukola puloteyina za G eziri wansi.
GHRP-R ekoleddwa etumbula okuwanyisiganya kwa nucleotide za guanosine mu kitundu kya G protein α ekiyungiddwa ku kyo, nga GDP ekyusiddwa ne GTP, ekivaako ekitundu kya G protein α okwekutula ku G protein βγ dimer. Dissociated G protein α subunit ne G protein βγ dimer zisobola okwongera okukola amakubo ag’enjawulo ag’okutambuza obubonero wansi, ne kivaako omuddirirwa gw’ebikolwa by’ebiramu mu butoffaali, okukkakkana nga kivuddeko okweyongera kw’okufulumya obusimu bw’okukula.
CJC-1295, nga synthetic growth hormone analog, eyamba mu kugejja, okutumbula ebinywa, okuzza obuggya olususu, okulongoosa otulo, n’okuwona ebiwundu. Ipamorelin ye pentapeptide ekoleddwa mu kika kya peptides ezifulumya obusimu bw’okukula (secretagogues). Kisitula okufulumya obusimu bw’okukula era kikwata ku nkola ez’enjawulo ez’omubiri, omuli okwanguya okufulumya amazzi mu lubuto, okulongoosa obubonero bw’okuzibikira ekyenda oluvannyuma lw’okulongoosebwa, okusitula okufulumya insulini, n’okuziyiza ebikolwa bya catabolic ebya glucocorticoids ku binywa by’amagumba n’amagumba. Okunoonyereza ku ngeri ebirungo bino ebibiri gye bikwataganamu kiyinza okuvaamu okukulaakulana okupya mu by’obulamu, eddagala ly’emizannyo, n’obujjanjabi bw’endwadde ezikwatagana nabyo.
Ekifaananyi 2 Emiwendo gya GH mu plasma okusinziira ku budde mu mbizzi oluvannyuma lwa iv okuweebwa dose ez’enjawulo eza ipamorelin.
Okukola amakubo g’okukyusa obubonero mu butoffaali
Phospholipase C - protein kinase C pathway (PLC - PKC pathway): Ekitundu kya G protein α ekikola kisobola okukola phospholipase C (PLC), esengejja phosphatidylinositol-4,5-bisphosphate (PIP2) ku luwuzi lw’obutoffaali mu babaka babiri abakulu ab’okubiri: inositol-1,4,5-trisphosphate (IP3) ne diacylglycerol (DAG). IP3 esaasaana mu cytoplasm, yeekwata ku IP3 receptors ku endoplasmic reticulum, era n’etumbula okufulumya kwa calcium ions (Ca 2+ ) okuva mu endoplasmic reticulum, ekivaako okweyongera amangu mu bungi bwa Ca 2+ mu butoffaali . DAG esigala ku luwuzi lw’obutoffaali n’okukola protein kinase C (PKC). PKC esobola okulungamya okwolesebwa kw’obuzaale obukwatagana nga ekola phosphorylating omuddirirwa gwa puloteyina eziri wansi w’omugga, gamba nga ensonga z’okuwandiika, bwe kityo n’etumbula okusengejja n’okufulumya obusimu bw’okukula. Ekirungo kya Ca⊃2;+ ekigulumivu mu butoffaali nakyo kisobola okukola butereevu ku bikuta ebifulumya okutumbula okufulumya obusimu bw’okukula.
Ekkubo lya mitogen-activated protein kinase (MAPK pathway): Ng’oggyeeko ekkubo lya PLC-PKC, Ipamorelin ekola ekkubo lya mitogen-activated protein kinase oluvannyuma lw’okukola GHRP-R okutumbula okufulumya obusimu obukula. G protein βγ dimer ekola ekirungo kya guanine nucleotide exchange factor (GEF), ekitumbula okukyusa GDP esibiddwa ku puloteyina ya Ras okudda mu GTP, bwe kityo ne kikola puloteyina ya Ras. Puloteeni ya Ras ekola eyongera okukola puloteyina ya Raf, ekola phosphorylate n’okukola mitogen-activated protein kinase kinase (MEK). Olwo MEK efuulibwa phosphorylated era n’ekola ekirungo ekiyitibwa extracellular signal-regulated kinase (ERK). Oluvannyuma lw’okuyingira mu nyukiliya y’obutoffaali, ERK ekola phosphorylates omuddirirwa gw’ensonga z’okuwandiika, nga Elk-1, okulungamya okwolesebwa kw’obuzaale obukwatagana n’okusengejja n’okufulumya obusimu bw’okukula, bwe kityo n’etumbula okukola n’okufulumya obusimu obukula.
Okulungamya ekitundu ky’omubiri ekiyitibwa hypothalamic-pituitary axis
Ekitundu kya hypothalamic-pituitary axis kikola kinene mu kulungamya okufulumya obusimu obukula. Ipamorelin tekoma ku kukola butereevu ku butoffaali bw’obusimu obukula mu nseke y’omu maaso okutumbula okufulumya obusimu bw’okukula naye era mu ngeri etali butereevu ekwata ku kufulumya obusimu bw’okukula okuyita mu kulungamya hypothalamus. GHRH ne somatostatin (SST) ebifulumizibwa hypothalamus birina ebikosa okutumbula n’okuziyiza ku kufulumya obusimu bw’okukula, okusinziira ku. Ipamorelin esobola okulung’amya mu ngeri etali butereevu okufulumya obusimu bw’okukula ng’ekyusakyusa okusengejja n’okufulumya GHRH ne SST mu busimu obuyitibwa hypothalamic neurons. Ipamorelin eyinza okuziyiza emirimu gy’obusimu bwa SST mu hypothalamus, okukendeeza ku kufuluma kwa SST, bwe kityo ne kikendeeza ku buziyiza bwa SST ku kufulumya obusimu obukula. Ipamorelin era esobola okutumbula okucamuka kw’obusimu bwa GHRH, okutumbula okufulumya GHRH, n’okwongera okusitula okufulumya obusimu bw’okukula. Kino ekifuga eky’emirundi ebiri ku hypothalamic-pituitary axis kisobozesa Ipamorelin okulungamya emitendera gy’okufulumya obusimu bw’okukula.
Omulimu gwa Ipamorelin mu kutumbula okufulumya obusimu bw’okukula
Okutumbula enkulaakulana n’enkulaakulana
Mu kiseera ky’okukula n’okukula kw’ebisolo, obusimu obukula bukola kinene mu kulungamya, era Ipamorelin akwata bulungi enkula n’enkula y’ebisolo ng’etumbula okufulumya obusimu obukula. Mu bisolo ebito, okukozesa Ipamorelin kyongera nnyo ku mutindo gw’okukula. Nga tutwala envunza ng’ekyokulabirako, oluvannyuma lw’okuweebwa ddoozi entuufu eya Ipamorelin, envunza ziraga okweyongera kw’obuzito mu bwangu, okweyongera n’okwawukana kw’ebipande by’okukula kw’amagumba, n’okwongera ku buwanvu bw’amagumba amawanvu. Kino kiyinza okuva ku kuba nti obusimu obukula busitula okukola ekirungo ekikula ekiringa insulini-1 (IGF-1) mu bitundu by’omubiri ng’ekibumba. IGF-1 etambula okuyita mu musaayi okutuuka mu bitundu ng’amagumba, n’etumbula okukula n’okwawukana kw’obutoffaali obuyitibwa chondrocytes, bwe kityo n’eyamba okukula kw’amagumba. Ipamorelin etumbula okufulumya obusimu bw’okukula, mu ngeri etali butereevu n’eyongera ku kukola IGF-1, bwe kityo n’ayanguyiza okukula n’okukula kw’amagumba.
Ipamorelin era ayamba enkula y’ebinywa. Obusimu bw’okukula butumbula okukola puloteyina, buziyiza okumenya kwa puloteyina, n’okwongera ku buzito bw’ebinywa. Mu kugezesa ebisolo, oluvannyuma lw’okuweebwa Ipamorelin, ebisolo byalaga ebiwuzi by’ebinywa ebinene n’amaanyi g’ebinywa ne geeyongera.
Ebikosa okulungamya ku nkyukakyuka y’emmere
Okulungamya enkyukakyuka ya glucose: Ipamorelin etumbula okufulumya obusimu bw’okukula, ng’akola ekikolwa ekimu eky’okulungamya ku nkyukakyuka ya glucose. Obusimu obukula bulina emirimu ebiri mu nkyukakyuka ya glucose. Ku mitendera gy’omubiri, obusimu bw’okukula busitula okufulumya insulini, butumbula okutwalibwa n’okukozesa glucose, era bukendeeza ku glucose mu musaayi. Ku bungi, obusimu obukula bulaga ekikolwa ekiziyiza insulini, okuziyiza okutwalibwa n’okukozesa glucose mu bitundu by’omubiri eby’okumpi, bwe kityo ne kyongera ku miwendo gya glucose mu musaayi. Ipamorelin mu ngeri etali butereevu ekwata ku bbalansi y’enkyukakyuka ya glucose ng’etereeza okufulumya obusimu bw’okukula. Mu bisolo ebya bulijjo, dose ezisaanidde eza Ipamorelin zisobola okukuuma glucose mu musaayi ku mutindo ogutali mutebenkevu, ekiyinza okuva ku kutumbula kwayo okufulumya obusimu obukula, nga kino nakyo kisitula okufulumya insulini okutuuka ku ddaala eritali limu, bwe kityo ne kitereeza glucose mu musaayi. Mu bikolwa by’ebisolo ebirina ssukaali, ebiva mu Ipamorelin biba bizibu nnyo; kiyinza okulongoosa obuziyiza bwa insulini nga kitereeza okufulumya obusimu bw’okukula, bwe kityo ne kikola akakwate akalungi ku kufuga glucose mu musaayi.
Okulungamya enkyukakyuka y’amasavu: Obusimu bw’okukula butumbula okumenya amasavu, kyongera ku fatty acid oxidation okusobola okukola amaanyi, n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu. Ipamorelin etumbula okufulumya obusimu bw’okukula, bwe kityo n’ekola ekikolwa kyayo eky’okulungamya ku nkyukakyuka y’amasavu. Mu kugezesa ebisolo, oluvannyuma lw’okuweebwa Ipamorelin, amasavu agali mu mibiri gy’ebisolo gakendeera naddala mu bitundu ng’olubuto. Kino kiri bwe kityo kubanga obusimu obukula bukola hormone-sensitive lipase (HSL) mu butoffaali bw’amasavu, ne butumbula okusaanuuka kw’amazzi mu triglycerides okufuuka asidi z’amasavu ne glycerol. Olwo asidi z’amasavu ziyingira mu mitochondria okusobola okukola β-oxidation okukola amaanyi. Obusimu bw’okukula era buziyiza okwawukana kw’obutoffaali bw’amasavu, ne bukendeeza ku muwendo gwabwo n’okwongera okukendeeza ku masavu mu mubiri. Ipamorelin, ng’etumbula okufulumya obusimu bw’okukula, ekola kinene mu kulungamya enkyukakyuka y’amasavu n’okufuga obuzito bw’omubiri.
Ebikosa okuddaabiriza n’okuzza obuggya ebitundu by’omubiri
Obusimu obukula bukola kinene nnyo mu kuddaabiriza ebitundu by’omubiri n’okuzza obuggya. Ipamorelin, nga etumbula okufulumya obusimu bw’okukula, etuwa embeera ennungi ey’okuddaabiriza ebitundu by’omubiri n’okuddamu okukola. Mu bitundu ebyonooneddwa, obusimu bw’okukula busobola okusitula okukula kw’obutoffaali n’okwawukana, okutumbula okusengejja ebitundu by’omubiri eby’ebweru w’obutoffaali nga kolagini, n’okwanguyiza okuwona kw’ebiwundu. Mu bikolwa by’obuvune ku lususu, oluvannyuma lw’okukozesa Ipamorelin, okukula kw’obusimu obuyitibwa fibroblast mu kifo ekiwundu kwanguyira, okuteekebwa kwa kolagini kweyongera, era obudde bw’okuwona ebiwundu bukendeera. Kino kiyinza okuva ku busimu bw’okukula obutumbula okufulumya kwa fibroblast okwa cytokines nga transforming growth factor-β (TGF-β), ekyongera okusitula okukula kw’obusimu obuyitibwa fibroblast n’okukola kolagini. Obusimu bw’okukula era butumbula okukula n’okusenguka kw’obutoffaali bw’emisuwa obuyitibwa endothelial cells, okwanguyiza okutondebwa kw’emisuwa emipya okusobola okuwa ebiriisa ebimala ne oxygen eri ebitundu ebyonooneddwa, bwe kityo ne kyanguya okuddaabiriza ebitundu. Omulimu gwa Ipamorelin mu kutumbula okuddaabiriza n’okuzza obuggya ebitundu by’omubiri gugifuula omuntu asuubiza okukozesebwa mu kujjanjaba abafunye obuvune, okulongoosa obuveera, n’emirimu emirala.
Okukozesa Ipamorelin mu kutumbula okufulumya obusimu bw’okukula
Ebiyinza okukozesebwa mu by’obusawo
Obujjanjabi bw’obusimu bw’okukula: Obutaba na busimu bw’okukula mbeera ereetebwa obutafulumya busimu bwa kukula bumala, emanyiddwa ng’obuwanvu obumpi n’okulwawo okukula n’okukula. Bw’ogeraageranya n’obujjanjabi obw’ekinnansi obw’okukyusa obusimu bw’okukula, Ipamorelin esitula okufulumya obusimu bw’okukula obw’omunda, okwewala ebimu ku bizibu ebikwatagana n’okukozesa obusimu bw’okukula obw’ebweru okumala ebbanga eddene. Okunoonyereza mu malwaliro kulaga nti mu balwadde abamu abalina obuzibu mu busimu bw’okukula, okukozesa eddagala lya Ipamorelin kyongera bulungi ku busimu bw’okukula, okwanguya okukula kw’obuwanvu, n’okutumbula omutindo gw’obulamu.
Eddagala eriweweeza ku kukaddiwa: Abantu bwe bakaddiwa, obusimu bw’okukula bukendeera mpolampola, ekintu ekikwatagana ennyo n’enkyukakyuka nnyingi mu mubiri eziva ku myaka. Ipamorelin, eyamba okufulumya obusimu bw’okukula, erina omulimu ogutali gumu mu mulimu gw’okulwanyisa okukaddiwa. Nga ayongera ku busimu bw’okukula, Ipamorelin eyinza okulongoosa enkola y’omubiri mu bakadde, okwongera ku binywa, okukendeeza amasavu okukuŋŋaanyizibwa, okutumbula amagumba, n’okulongoosa olususu okunyirira. Okugezesebwa mu malwaliro kulaga nti abakadde abakozesa Ipamorelin mu ddoozi ezisaanidde bafuna okulongoosa mu nkola y’omubiri, sitamina, n’embeera y’ebirowoozo.
Okutumbula okuwona kw’ebiwundu: Ipamorelin etumbula okuddaabiriza ebitundu by’omubiri n’okuddamu okukola ng’esitula okufulumya obusimu obukula. Mu nkola y’obusawo, eri abalwadde abalina obuvune obumu, gamba ng’okwokya oba okumenya, okukozesa Ipamorelin kiyinza okwanguya ebiwundu okuwona n’okukendeeza ku bizibu ebibaawo. Mu balwadde abayokebwa, Ipamorelin esobola okutumbula epithelialization ku ngulu w’ekiwundu n’okukendeeza ku kutondebwa kw’enkovu; mu balwadde abamenyese, kisobola okutumbula okutondebwa kw’amagumba n’okwanguyiza okuwona kw’amagumba. Kino kiwa enkola empya ey‟obujjanjabi obw‟obuyambi obw‟okuddukanya obuvune, nga erina obusobozi okutumbula ebiva mu bujjanjabi.
Okukozesebwa mu ddagala ly’emizannyo
Olw’obusobozi bwayo okusitula okufulumya obusimu bw’okukula, esobola okwongera ku binywa, okutumbula omutindo gw’emizannyo, n’okwanguyiza okuwona oluvannyuma lw’okukola dduyiro. Mu bannabyamizannyo abeenyigira mu kutendekebwa okw’amaanyi, Ipamorelin eyinza okubayamba okuddamu amangu amaanyi g’omubiri, okukendeeza ku bukoowu bw’ebinywa, n’okukendeeza ku bulabe bw’okufuna obuvune. Mu bannabyamizannyo abagumiikiriza, Ipamorelin eyinza okutumbula okugumira dduyiro ng’etumbula enkyukakyuka y’amasavu; mu bannabyamizannyo ab’amaanyi, kiyinza okwongera ku maanyi g’ebinywa n’amaanyi.
Mu bufunzi
Mu bufunze, nga pentapeptide etumbula okufulumya obusimu bw’okukula, Ipamorelin eraga emirimu emikulu mu kukula n’okukula, okulungamya enkyukakyuka mu mubiri, okuddaabiriza ebitundu, n’ebitundu ebirala eby’enjawulo eby’okukozesa.
Ensonda
[1] Papak M. Ipamorelin - okuzimba omubiri gwe, 2016[C]. https://api.semanticscholar.org/CorpusID:78470780. Enkola y’okukuuma obutonde bw’ensi
[2] Adeghate E, Ponery AS, Emirates U A. ORIGINALARTICLE Enkola y’okufulumya insulini ereetebwa ipamorelin okuva mu kyenda ky’envunza eza bulijjo ne ssukaali, 2004[C]. https://api.semanticscholar.org/CorpusID:74621068. Enkola y’okukuuma obutonde bw’ensi
[3] Raun K, Hansen B. S., Johansen N. L., n’abalala. Ipamorelin, ekirungo ekisooka okulonda obusimu bw’okukula.[J]. European Journal of Endocrinology, 1998,139 5:552-561.
Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
