1kits (Ebipipa 10) .
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▎ GHRP-2 kye ki?
GHRP-2 (Growth Hormone-Releasing Peptide-2) kirungo kya peptide ekikoleddwa mu ngeri ey’enjawulo ekikwatagana n’okukola ku bikwata peptide ebifulumya obusimu bw’okukula (GHSR) mu nkola y’obusimu obw’omu maaso n’obusimu obw’omu makkati, bwe kityo ne kitumbula okusengejja n’okufulumya obusimu bw’okukula obw’omunda (GH). Ekikolwa kyayo tekikwata ku kkubo ly’obusimu obufulumya obusimu bw’okukula (GHRH), ekigisobozesa okutumbula okufulumya GH oba nga yeetongodde oba mu ngeri ey’okukolagana. Kikola bulungi mu mbeera zombi eza basal ne stimulated era okusinga ekozesebwa mu kunoonyereza ku growth hormone axis ne related metabolic regulation.
▎ ya GHRP-2 Enzimba
Ensibuko: PubChem |
Omutendera: AXAWFK Ensengekera ya molekyu: C 45H 55N 9O6 Obuzito bwa molekyu: 817.98 g/mol Ennamba ya CAS:158861-67-7 PubChem CID:6918245 Ebigambo ebikwatagana: Pralmorelin;pralmorelina;KP-102;pralmoreline |
▎ GHRP-2 Okunoonyereza ku
Ensibuko y’okunoonyereza ku GHRP-2 eri etya?
Obusimu bw’okukula bukola kinene nnyo mu kukula kw’omuntu, enkula y’omubiri, n’okutebenkeza enkyukakyuka mu mubiri. Bannasayansi baludde nga banoonya ebintu ebisobola okulung’amya obulungi okufulumya kwayo. Growth hormone-releasing peptides (GHRPs), ekika kya oligopeptides ezikoleddwa mu butonde ezisitula okufulumya obusimu bw’okukula, zivuddeyo ng’ekintu ekikulu mu kunoonyereza.
GHRP-2 ekoppa ekikolwa kya ghrelin nga yesiba ku ghrelin receptor, okukola amakubo g’obubonero okusobola okusitula obulungi GH okufuluma. Kiraga obusobozi mu kuzuula n’okujjanjaba obutaba na busimu bw’okukula, okuyingira mu nsonga z’okwetamwa okulya, n’okukuuma obutayonoonebwa ebitundu by’omubiri, ekivuga okunoonyereza okw’obwegendereza ku nkola yaakyo n’enkozesa yaakyo.
Enkola ki ey’okukola ku GHRP-2?
Okulungamya Okufuluma kw’obusimu bw’okukula
Okukola ku kitundu kya Hypothalamic-Pituitary Axis:
GHRP-2 esitula okufulumya obusimu bw’okukula (GH) okuyita mu kikolwa eky’enjawulo eky’okujjulizagana emirundi ebiri nga kigendereddwamu byombi hypothalamus ne pituitary gland (Bowers CY). Ku ddaala lya pituitary, GHRP-2 yeekwata ku kirungo ekikwata obusimu obufulumya obusimu bw’okukula (GHS-R). Nga yeesibye ku GHS-R, GHRP-2 etandikawo ekibinja ky’ebintu ebiraga obubonero mu butoffaali. Okugeza, ekola phospholipase C (PLC), ekola ku kusengejja amazzi ga phosphatidylinositol-4,5-bisphosphate (PIP2) ku luwuzi lw’obutoffaali okufuuka inositol trisphosphate (IP3) ne diacylglycerol (DAG). IP3 etumbula okufulumya kwa calcium ion okuva mu endoplasmic reticulum, ate DAG ekola protein kinase C (PKC), okukkakkana nga kivaako okufulumya GH (Roh SG,). Mu kunoonyereza okwakolebwa nga bakozesa obutoffaali bw’ente, GHRP-2 ku bungi obw’enjawulo (10−⊃1;⊃3; okutuuka ku 10−7 M) yayongera nnyo ku kusengejja GH (P < 0.05), ekiraga nti GHRP-2 ekola obutereevu okusikirizibwa ku kufulumya GH obutoffaali bw’ennyindo [1] ..
Okukolagana n’obusimu obufulumya obusimu bw’okukula (GHRH):
GHRP-2 eraga ebikolwa ebikwatagana ne GHRH mu kusitula okufulumya GH. Bwe ziweebwa wamu mu butoffaali bwa pituitary, zikola nga ziyita mu makubo ag’enjawulo ag’obubonero agasembayo okukwatagana okutumbula okufulumya kwa GH. Okunoonyereza kulaga nti GHRH okusinga ekola adenylate cyclase (AC), n’esitula emiwendo gya cAMP mu butoffaali oluvannyuma okukola protein kinase A (PKA), bwe kityo n’etumbula okuwandiika kw’obuzaale bwa GH n’okusengejja/okufulumya GH. Okwawukana ku ekyo, GHRP-2 ekola ebikolwa byayo ng’eyita mu kkubo lya PLC-IP3/DAG-PKC eryayogeddwako waggulu. Enkolagana yaabwe ey’okukwatagana eyongera nnyo ku kufulumya GH. Mu kugezesa obutoffaali bw’endiga obuyitibwa pituitary cell, zombi GHRH (10 nM) ne GHRP-2 (100 nM) ssekinnoomu zayongera ku miwendo gya GH mRNA n’okufulumya GH mu ngeri eyeesigama ku budde mu ssaawa 0.5–2; ekikolwa kino kyayongerwa nnyo bwe kyagattibwa [2] ..
Okulungamya okufuluma kw’obusimu bw’okukula:
GHRP-2 esitula okufulumya obusimu bw’okukula (GH) okuyita mu kikolwa eky’enjawulo eky’okujjuliza emirundi ebiri, mu kiseera kye kimu nga kitunuulira hypothalamus ne pituitary gland (Bowers CY). Ku ddaala lya pituitary, GHRP-2 yeekwata ku kirungo ekikwata obusimu obufulumya obusimu bw’okukula (GHS-R). Nga yeesibye ku GHS-R, GHRP-2 etandikawo ekibinja ky’ebintu ebiraga obubonero mu butoffaali. Okugeza, ekola phospholipase C (PLC), ekola ku kusengejja amazzi ga phosphatidylinositol 4,5-bisphosphate (PIP2) ku luwuzi lw’obutoffaali okufuuka inositol trisphosphate (IP3) ne diacylglycerol (DAG). IP3 etumbula okufulumya kwa calcium ion okuva mu endoplasmic reticulum, ate DAG ekola protein kinase C (PKC), okukkakkana nga kivaako okufulumya GH (Roh SG,). Mu kunoonyereza okwakolebwa nga bakozesa obutoffaali bw’ente, GHRP-2 ku bungi obw’enjawulo (10−⊃1;⊃3; okutuuka ku 10−7 M) yayongera nnyo ku kusengejja GH (P < 0.05), ekiraga nti GHRP-2 ekola obutereevu okusikirizibwa ku kufulumya GH obutoffaali bw’ennyindo [1] ..
Ebikosa Obujjanjabi ku Anorexia:
Ku balwadde abalina obulwadde bw’okwetamwa okulya, okuweebwa GHRP-2 mu nnyindo kyongera okuwulira enjala n’okulya emmere, kikendeeza ku kukkuta amangu, n’okulongoosa obubonero bw’okukendeera kwa sukaali. Oluvannyuma lw’emyezi 14 nga baweebwa GHRP-2, abalwadde baagenda beeyongera kkiro 6.7 mu mubiri. Enkola eno eyinza okuzingiramu GHRP-2 okukola nga ghrelin receptor agonist okukoppa ebikolwa bya ghrelin, bwe kityo n’ekyusakyusa ekifo we bagala okulya n’okulongoosa enneeyisa y’abalwadde mu kulya n’embeera y’endya [3]..

Ekifaananyi 1 (A) Enkyukakyuka mu buzito bw’omubiri, ebinywa, n’amasavu oluvannyuma lw’okujjanjabwa n’obusimu bw’okukula obufulumya peptide-2 (GHRP-2). Amasavu n’obuzito bw’ebinywa byakeberebwa nga bakozesa enkola ya bio-impedance. Parameters zonna zeeyongera mpolampola, nga obuzito bw’omubiri n’amaanyi agayingira buli lunaku birinnya −1.5 ku 2.4 kg ne 12% ku 36%, respectively, oluvannyuma lw’okufuyira ghrelin. (B) Enkyukakyuka mu miwendo gy’obusimu bw’okukula (GH) n’ekirungo ky’okukula ekiringa insulini 1 (IGF-1) oluvannyuma lw’okujjanjabwa GHRP-2. GH yakendeera ate IGF-1 n’eyongera oluvannyuma lw’emyezi 12. (C) Enkyukakyuka mu mbeera y’emmere. Retinol binding protein (RBP) ne total protein (TP) byalinnya mangu, nga albumin (Alb) yeeyongera oluvannyuma lw’emyezi 4. Ebipimo bino byeyongera oluvannyuma lw’emyezi 12. (D) Enkyukakyuka mu miwendo gya acyl ghrelin (AG) ne des-acyl ghrelin (DAG) oluvannyuma lw’okuweebwa GHRP-2. DAG ne AG ez’okusiiba zeeyongera, era omugerageranyo gwa DAG/AG gwakendeera oluvannyuma lw’emyezi 10. BW; obuzito bw’omubiri.
Ensibuko: PubMed [3] .
Biki ebikozesebwa mu by’obujjanjabi ebya GHRP-2?
Okuzuula obuzibu bw’obusimu obukula: GHRP-2 ekozesebwa mu bujjanjabi ng’ekirungo ekizuula obuzibu bw’obusimu obukula. Ku bbula ly’obusimu bw’okukula, okukebera okw’ensi yonna okusooka kwe kukebera okugumira insulini (ITT). Wabula olw’okuba esobola okuleeta ebizibu eby’amaanyi, tekikkirizibwa ku balwadde abamu. Okunoonyereza kuleese ekiteeso ky’okukozesa GHRP-2 okuzuula obuzibu bw’obusimu bw’okukula kw’abantu abakulu (GHD). Okunoonyereza kuno kwawandiisa abantu 77 abalamu n’abalwadde 58 nga balina peak GH < 3 μg/L nga bwe kyazuulibwa ITT. Abagezesebwa bonna baafuna empiso ya 100 μg GHRP-2 mu misuwa, oluvannyuma ne batwalibwa omusaayi mu ssaawa 2 ezaddirira. Emiwendo gya GH gyapimibwa nga bakozesa enkola ya immunoradiometric assay. Ebivuddemu biraga nti abantu bonna baayoleka peak serum GH mu ddakiika 60 oluvannyuma lw’okuweebwa GHRP-2. GH responsiveness to GHRP-2 tekyakosebwa kikula kya muntu. Wadde ng’okuddamu kwali wansi katono mu bantu abakadde n’abantu abagejjulukuka, kino tekyataataaganya kuzuula GHD. Okugezesa okuddiŋŋana kwalaga nti enkola eno esobola okuddamu okukola obulungi. Nga okozesa GHRP-2 okuzuula GHD, omuwendo gw’okusalako ogwa 15 μg/L gukwatagana n’omuwendo gw’okuzuula ogwa 3 μg/L mu ITT, ekiraga nti okuteekawo okusalako okutuufu okw’obungi bwa GH mu musaayi kizuula mu ngeri eyesigika ebbula ly’obusimu bw’okukula obw’amaanyi [4]..
Obujjanjabi bw’obulwadde bw’okwetamwa okulya: Ku balwadde abalina ebyafaayo by’obulwadde bw’okwetamwa okulya, GHRP-2 eyinza okukiikirira ekirungo ekisuubiza eky’obujjanjabi. Okunoonyereza okumu kwaweebwa GHRP-2 mu nnyindo nga buli mmere tennalya okumala omwaka gumu eri omulwadde eyalina ebyafaayo by’emyaka 20 ng’alina obulwadde bw’okwetamwa okulya. Nga tannajjanjabwa, wadde ng’okutya omulwadde okulya n’okwagala okubeera omugonvu kwali kukendedde okuyita mu bujjanjabi obwaliwo emabega, obutakola bulungi mu lubuto bwalemesa okulya emmere okweyongera n’okugejja. Obubonero bwalimu okusesema oluvannyuma lw’okulya, okuziyira, okuzibikira wansi w’ekyenda, n’okukendeeza ku sukaali mu musaayi. Oluvannyuma lw’okuweebwa GHRP-2, omulwadde yafuna enjala okweyongera n’emmere gye yalya, okukkuta amangu, obubonero bwa sukaali mu musaayi ne butereera, era obuzito bw’omubiri ne bweyongera mpolampola kkiro 6.7 (okuva ku kkiro 21.1 okutuuka ku kkiro 27.8) mu myezi 14 ng’atandika obujjanjabi. Obukoowu n’amaanyi g’ebinywa byalongooka, emirimu gy’omubiri n’obwongo gyeyongera, era tewali bikolwa bya maanyi byalabibwa nga bamuwadde mu nnyindo okumala ebbanga eddene. Kino kiraga nti GHRP-2 eyinza okuba eddagala eddungi erijjanjaba abalwadde abalina obulwadde bw’okwetamwa okulya ennyo [3]..
Okukendeeza ku buzibu obuva ku kwokya: Oluvannyuma lw’okwokya ennyo, okweyongera kw’okukola obusimu obuyitibwa catabolic hormones ne inflammatory cytokines ku mabbali g’okukendeera kw’obusimu obuyitibwa anabolic hormone kivaako okukola ennyo mu mubiri, okukendeeza ku mubiri omugonvu, n’okusaasaana kw’ebinywa. Wadde ng’obujjanjabi obw’enjawulo nga dduyiro n’okukozesa obusimu obukola ku busimu obuyitibwa anabolic hormones (insulin, growth hormone, IGF-I, oba steroids) buteeseddwa oba bukozesebwa, ebivaamu bisigala nga si birungi. Ebivudde mu kugezesa biraga nti ekirungo ekipya ekyawulwamu anti-cachexia peptide ghrelin kikendeezebwa mu nvunza oluvannyuma lw’okwokya. Exogenous ghrelin esobola okuzzaawo okugejja ng’eyongera ku mmere n’okutumbula ebinywa mu mbeba. Era kikendeeza nnyo ku kuvunda kwa puloteyina y’ebinywa by’amagumba mu nvunza eziyokebwa nga ezza mu mbeera eya bulijjo okulaga mRNA y’ebinywa eya E3 ubiquitin ligase, MuRF1, ne MAFbx. Ekitundu ekitono eky’obulamu bwa ghrelin kikoma ku kukozesebwa kwayo mu bujjanjabi. Okwawukana ku ekyo, synthetic hexapeptide growth hormone-releasing peptide 2 (GHRP-2) ye GHRP receptor agonist enywevu era ey’amaanyi eyongera ku buzito bw’omubiri mu nvunza, eraga ebikolwa eby’okulwanyisa okuzimba mu nvunza ezirina endwadde z’enkizi, n’okulongoosa catabolic metabolism mu balwadde abali mu mbeera embi. GHRP-2 ekwata bulungi ku buzito bw’omubiri, emmere gye balya, n’okumenya kwa puloteyina y’ebinywa by’amagumba mu biwuka ebyokeddwa, okukendeeza ku butakola bulungi obuva ku kwokya [5].
Mu bufunzi
GHRP-2 ekola okufulumya obusimu bw’okukula nga esitula amakubo g’obubonero agakwatagana okuyita mu kikolwa kyayo ku GHS-R munda mu kisenge kya hypothalamic-pituitary. Mu by’obujjanjabi, esobola okuzuula obutaba na busimu bw’okukula n’okujjanjaba embeera ng’okulya emmere, obuvune bw’ekibumba obw’amaanyi (septic acute kidney injury), n’obutakola bulungi oluvannyuma lw’okwokya, ate nga era eraga eddagala eriweweeza ku bulumi n’okuziyiza obuwuka obuleeta obulwadde.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Haruta I musawo-ssaayansi eyeegattira mu kitongole ky’obusawo obw’omunda obw’eby’omutwe mu yunivasite y’e Kagoshima Graduate School of Medical and Dental Sciences mu Japan. Okunoonyereza kwe mu kuvvuunula kussa essira ku kuyingirira endocrine ne metabolic interventions mu severe anorexia nervosa. Haruta I ewandiikiddwa mu kiwandiiko ekijuliziddwa [3].
▎ Ebiwandiiko Ebikwatagana
[1] Roh SG, He ML, Matsunaga N, Hidaka S, Hidari H. Enkola z’okukola kw’obusimu bw’okukula obufulumya peptide-2 mu butoffaali bw’ente obuyitibwa pituitary cells. Journal of Sayansi w’Ebisolo 1997; 75 (10): 2744-2748.DOI: 10.2527/1997.75102744x.
[2] Yan M, Hernandez M, Xu R, Chen C. Enkola y’obujjanjabi bwa GHRH ne GHRP-2 mu vitro ku kufulumya GH n’emiwendo gya GH, pituitary transcription factor-1, GHRH-receptor, GH-secretagogue-receptor ne somatostatin receptor mRNAs mu butoffaali bw’ennywanto y’ente. Ekitabo kya Bulaaya eky’eby’endwadde z’omu lubuto 2004; 150 (2): 235-242.DOI: 10.1530 / eje.0.1500235.
[3] Haruta I, Fuku Y, Kinoshita K, n’abalala. Okusiiga peptide-2 mu nnyindo mu nnyindo okumala omwaka gumu kitereeza obuzito bw’omubiri n’okukendeeza ku sukaali mu mulwadde alina obusimu bw’okwetamwa okulya obugonvu ennyo. Journal of Cachexia Sarcopenia n’ebinywa 2015; 6(3): 237-241.DOI: 10.1002/jcsm.12028.
[4] Chihara K, Shimatsu A, Hizuka N, Tanaka T, Seino Y, Katofor Y. Okugezesebwa okwangu okuzuula nga tukozesa GH-releasing peptide-2 mu bantu abakulu ababulwa GH. Ekitabo kya Bulaaya eky’eby’endwadde z’omu lubuto 2007; 157(1): 19-27.DOI: 10.1530/EJE-07-0066.
[5] Balasubramaniam A, Joshi R, Mukwano LA, James JH. GHRP-2 ekendeeza ku buzibu obuva ku kwokya mu biwuka. Enkulaakulana mu ddagala ery’okugezesa n’ebiramu 2009; 611: 571-572.DOI: 10.1007/978-0-387-73657-0_251.
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.