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1kits (Ebipipa 10) .
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▎ Enzimba ya Ipa
Ensibuko: PubChem |
Omutendera: XHXFK Ensengekera ya molekyu: C 38H 49N 9O5 Obuzito bwa molekyu: 711.9 g/mol Ennamba ya CAS: 170851-70-4 PubChem CID: 9831659. Omuntu w’abantu Ebigambo ebikwatagana: NNC-26-0161;UNII-Y9M3S784Z6;Ipa ACETATE |
▎ kwa Ipa Okunoonyereza
Ipa alina okunoonyereza ku ngeri ki?
Okulwawo okufulumya amazzi mu lubuto mbeera ya bulijjo, era mu kiseera kino, waliwo obujjanjabi obutono obukola obulungi. Okunoonyereza kuzudde nti Ipa, nga synthetic peptidomimetic, ekola ku ghrelin receptor era eyinza okuba n’ekikolwa eky’obujjanjabi ku kulwawo okufulumya amazzi mu lubuto. Mu kunoonyereza okwakolebwa ku nkola y’ebiwuka ey’okuzimba olubuto, okusannyalala kw’olubuto kwaleetebwa okulongoosebwa mu lubuto n’okukozesa ebyenda, era kyazuulibwa nti Ipa esobola okwanguya okufulumya amazzi mu lubuto [1]..
Ileus oluvannyuma lw’okulongoosebwa kusoomoozebwa kwa maanyi mu nkola y’obujjanjabi, nga temuli nkola nnungi ez’okuddukanya. Ghrelin receptor stimulation erina ekikolwa ekitumbula okutambula ku bitundu byombi ebya waggulu n’ebya wansi eby’enkola y’olubuto. Nga ghrelin receptor agonist, Ipa erina omugaso oguyinza okukozesebwa mu kujjanjaba ileus oluvannyuma lw’okulongoosebwa. Okugeza, mu kunoonyereza, okunoonyereza okusuubirwa, okwa randomized, controlled proof-of-concept okunoonyereza kwakolebwa ku balwadde abalongoosebwa ekyenda oluvannyuma lw’okulongoosebwa olubuto okwekenneenya obukuumi n’obulungi bwa Ipa [2]..
Ipa eri mu peptides ezifulumya obusimu bw’okukula (GHRPs), nga eno ye pentapeptide ey’obutonde esobola okusitula okufulumya obusimu bw’okukula okuva mu hypothalamus ne pituitary gland. Obusimu obukula bukola kinene mu kukula kw’omubiri, okuddaabiriza, n’okukyusakyusa mu mubiri, kale omulimu gwa Ipa mu kulungamya obusimu bw’okukula nagwo gusikiriza abantu bangi [3]..
Olw’omugaso gwayo oguyinza okubaawo mu kujjanjaba okulwawo okuva mu lubuto, ileus oluvannyuma lw’okulongoosebwa, n’omulimu gwayo nga peptide efulumya obusimu bw’okukula, Ipa esikiriza okunoonyereza okunene.
Enkola y’okukola kwa Ipa eri etya?
1. Okusitula okufulumya obusimu bw’okukula:
Ipa ya peptides ezifulumya obusimu bw’okukula (GHRPs), ezisobola okusitula okufulumya obusimu obukula okuva mu hypothalamus ne pituitary gland. Okugezesa mu vitro ne in vivo, Ipa eraga amaanyi mangi n’obulungi mu kufulumya obusimu bw’okukula. Okugeza, mu kunoonyereza, amaanyi n’obulungi bwa Ipa mu kufulumya obusimu bw’okukula okuva mu butoffaali bw’envunza obusookerwako obw’envunza byali bifaanagana n’ebya GHRP-6 [3] . Enkola yaayo ey’okukola kwe kusitula okufulumya obusimu bw’okukula nga ekola ku bikwata ebiringa GHRP. Okuyita mu kwekenneenya eddagala, kikakasiddwa nti okufaananako GHRP-6, Ipa esitula okufulumya obusimu bw’okukula okuyita mu bikwata ebiringa GHRP.
2. Ebikosa enkola y’olubuto n’ekyenda
Okwanguya okufulumya amazzi mu lubuto:
Mu bikolwa by’ebiwuka, Ipa esobola okwanguya okufulumya amazzi mu lubuto. Okulongoosa olubuto kivaako okulwawo okufulumya amazzi mu lubuto, naye oluvannyuma lw’okuweebwa Ipa (0.014 μmol/kg mu misuwa), okufulumya amazzi mu lubuto kwanguyirwa nnyo. Ipa esitula okukonziba kw’olubuto n’okwanguyiza okufulumya amazzi mu lubuto ng’eyita mu nkola etabaganyizibwa okukola kw’ekirungo kya ghrelin, ekizingiramu obusimu obusikiriza obuyitibwa cholinergic excitatory neurons (Greenwood-Van Meerveld B, 2012).
Okulongoosa obubonero bw’obulwadde bwa ileus oluvannyuma lw’okulongoosebwa:
Mu bikolwa by’ebiwuka eby’obulwadde bwa ileus oluvannyuma lw’okulongoosebwa, Ipa eyinza okulongoosa obubonero. Oluvannyuma lw’okuweebwa Ipa oluvannyuma lw’okulongoosebwa, ddoozi emu eya Ipa (1mg/kg) oba GHRP-6 (20μg/kg) esobola okukendeeza ku budde bw’okusooka okufulumya omusulo. Okuddiŋŋana okugaba Ipa (0.1 oba 1mg/kg) kiyinza okwongera ennyo ku musulo ogukuŋŋaanyiziddwa, emmere gye balya, n’okugejja [4]..
3. Ebikosa okufulumya insulini
Ipa esobola okusitula okufulumya insulini mu bitundutundu by’ebitundu by’olubuto eby’envunza eza bulijjo n’eza ssukaali. Okweyongera kw’okufulumya insulini okuleetebwa Ipa kuyinza okuziyizibwa ennyo diltiazem, yohimbine, propranolol, oba okugatta atropine, propranolol, ne yohimbine. Mu nvunza ezirina ssukaali, atropine esobola okukendeeza ennyo ku kufulumya insulini okuleetebwa Ipa, naye ekikolwa kino tekirabibwa mu nvunza eza bulijjo. Kino kiraga nti Ipa esitula okufulumya insulini okuyita mu mukutu gwa calcium n’amakubo agakwata adrenergic [5]..
4. Okukendeeza ku bulumi
Mu bikolwa eby’okugezesa eby’obuzibu bw’omubiri obutazimba n’obusimu obuyitibwa somatic mechanical allodynia, Ipa, nga peripherally restricted ghrelin receptor agonist, esobola okukendeeza ennyo ku colonic hypersensitivity ne somatic allodynia. Enkola yaayo ey’okukola etabaganyizibwa ekirungo ekikwata ghrelin, era ekikolwa kino eky’okuziyiza obuwuka kiyinza okuziyizibwa ekiziyiza ekikwata ghrelin H0900 [6]..
Alaga ekikolwa kya Ipa ku kufulumya insulini okuva mu bitundutundu by’ebitundu by’olubuto eby’envunza eza bulijjo n’eza ssukaali.
Ensibuko:PubMed [5] .
Biki ebikozesebwa mu Ipa?
1. Okutumbula okufulumya obusimu bw’okukula
Ipa esobola okusitula okufulumya obusimu obukula okuva mu hypothalamus ne pituitary gland. Obusimu obukula bukola kinene mu mubiri gw’omuntu, omuli okutumbula okukola puloteyina, okukula kw’obutoffaali, n’okuddaabiriza ebitundu by’omubiri. N’olwekyo, Ipa esobola okukozesebwa okujjanjaba obutaba na busimu bw’okukula oba endwadde endala ezikwatagana n’obutakola bulungi mu busimu bw’okukula [7]..
2. Okulongoosa enkola y’omu lubuto n’ekyenda
Okwanguya okufulumya amazzi mu lubuto:
Mu bikolwa by’ebiwuka, Ipa eyanguya okufulumya eby’omu lubuto mu bikolwa by’ekirungo kya ileus oluvannyuma lw’okulongoosebwa okuyita mu nkola etabaganyizibwa okukola kw’obusimu bw’okukula obufulumya peptide receptor, nga kuzingiramu obusimu obusiikuula cholinergic [1] . Okulongoosa olubuto kivaako okulwawo okufulumya amazzi mu lubuto, era okugaba Ipa kiyinza okukendeeza ennyo ku kitundu ky’emmere esigadde mu lubuto, bwe kityo ne kitereeza entambula y’olubuto.
Okutumbula obulwadde bw’olubuto n’ekyenda:
Mu bikolwa by’ebiwuka eby’obulwadde bwa ileus oluvannyuma lw’okulongoosebwa, Ipa eyinza okulongoosa obubonero bw’abalwadde. Okugeza, mu nkola y’envunza, Ipa esobola okukendeeza ku budde bw’okusooka okufulumya omusulo oluvannyuma lw’okulongoosebwa, okwongera ku musulo ogufuluma, okulya emmere, n’okugejja [4] . Okuddiŋŋana okugaba Ipa kiyinza okwongera ennyo ku musulo ogukuŋŋaanyiziddwa, emmere gye balya, n’okugejja, ekiraga nti ekola bulungi mu kulungamya ku nkola y’olubuto n’ekyenda.
3. Okumalawo obulumi
Okumalawo obulumi mu bitundu by’omubiri n’omubiri:
Okunoonyereza kulaga nti Ipa, ng’ekirungo ekifulumya obusimu bw’okukula ekifulumya peptide receptor agonist, erina obusobozi obuziyiza obuwuka obuleeta endwadde. Mu bikolwa eby’okugezesa ebitaliiko kuzimba kwa bitundu by’ekyenda ekinene, Ipa esobola okukendeeza ennyo ku buzibu bw’ebitundu by’omubiri ebitali bizimba n’obusimu obuyitibwa somatic mechanical allodynia [6]..
Enkola yaayo ey’okukola eyinza okuba nga etabaganyizibwa ekirungo ekifulumya obusimu bw’okukula ekifulumya peptide, okwetaba mu kulungamya okuwuliziganya okw’omubiri n’omubiri, okuwa enkola empya eyinza okujjanjaba obulumi obw’amaanyi obw’omu bitundu by’omubiri n’obw’omubiri.
Biki ebigenda mu maaso mu kunoonyereza kwa Ipa mu kujjanjaba obutaba na busimu bw’okukula?
Obutabeera na busimu bw’okukula bulwadde obuva ku busimu obukula obutafulumya kimala okuva mu nseke y’omu maaso (anterior pituitary gland), ekiyinza okukosa enkula n’enkula y’abaana n’enkyukakyuka y’omubiri gw’abantu abakulu. Mu myaka egiyise, Ipa, ng’ekirungo ekifulumya obusimu bw’okukula, kifunye okufaayo okunene mu kujjanjaba obutaba na busimu bw’okukula. Wammanga ye nkulaakulana y’okunoonyereza ekwatagana eya Ipa mu kujjanjaba obutaba na busimu bw’okukula.
1. Enkola y’okusitula eya Ipa ku kufulumya obusimu bw’okukula
Ipa esobola okusitula okufulumya obusimu bw’okukula. Okunoonyereza kulaga nti Ipa esobola okukola mu ngeri ey’okukwatagana n’obusimu obufulumya obusimu obukula (GHRH) okutumbula okufulumya obusimu bw’okukula [8] . Mu kugezesa ebisolo, oluvannyuma lw’ennaku 21 ez’obujjanjabi obutawona ne Ipa mu nvunza enkazi ento, bw’ogeraageranya n’ekibinja ekifuga, okufuluma kw’obusimu obukula mu basal mu buwangwa bwa monolayer obw’obutoffaali bwa pituitary kweyongera. Mu kiseera kye kimu, Ipa ne GHRH zisobola okusitula okufulumya obusimu bw’okukula okuva mu butoffaali bwa pituitary obukuziddwa mu vitro. Wabula, mu kibinja kya GHRH nga tebannaba kujjanjabwa, okuddamu kw’obusimu bw’okukula obuddirira ku kusikirizibwa tekyanywezebwa, ate mu kibinja ekya Ipa nga tebannaba kujjanjabwa, tewaaliwo kintu ng’ekyo eky’okukendeeza ku buzibu, ekiraga nti Ipa teviirako kukendeeza ku busimu bw’okuddamu mu nvunza enkazi ento [8]..
2. Enkola ya Ipa ku kugejja
Okuweebwa Ipa okumala ebbanga eddene kisobola bulungi okwongera ku buzito bw’envunza enkazi ento. Okulondoola buli lunaku kulaga nti ebitundu ku kikumi eby’okugejja mu kibinja kya Ipa nga tebannaba kujjanjabwa n’ekibinja kya GHRH nga tebannaba kujjanjabwa biri waggulu okusinga mu kibinja ekifuga [8] . Kino kikwatagana n’okuba nti Ipa eyamba okufulumya obusimu bw’okukula, nga kino nakyo kitumbula okukola puloteyina n’okukula kw’obutoffaali.
3. Enkola ya Ipa ku kutondebwa kw’amagumba
Mu nkola y’envunza enkuze, kizuuliddwa nti ekirungo ekifulumya obusimu bw’okukula ekya Ipa kisobola okuziyiza ebikolwa bya catabolic ebiva mu glucocorticoids (GC) ku binywa by’amagumba n’amagumba. Bw’ogeraageranya n’ekibinja ekyafukibwa GC yokka, mu bisolo ebyafukibwa GC ne Ipa byombi, okusika omuguwa okusinga obunene okw’ekinywa ky’ennyana kweyongera nnyo, era omutindo gw’okutondebwa kw’amagumba g’omu lubuto gweyongera emirundi ena [8, 9] . Kino kiraga nti Ipa erina akakwate akalungi ku kukuuma amaanyi g’ebinywa n’okutumbula okutondebwa kw’amagumba, era eyinza okuyamba okuziyiza ebizibu ng’okuzimba amagumba mu balwadde abalina obuzibu bw’obusimu bw’okukula.
4. Enkola ya Ipa ku nkola y’olubuto n’ekyenda
Nga selective growth hormone-releasing hormone agonist ne growth hormone-releasing peptide receptor agonist, Ipa yalaga obulungi bw’obujjanjabi mu model y’ebibe ey’okusannyalala kw’ekyenda oluvannyuma lw’okulongoosebwa. Okuweebwa omulundi gumu Ipa oba growth hormone-releasing peptide (GHRP)-6 kyakendeeza ku budde okutuuka ku kyenda ekisooka oluvannyuma lw’okulongoosebwa, naye tekyalina kye kyakola ku musulo ogukuŋŋaanyiziddwa, okulya emmere, oba okugejja. Ipa eyongera ku musulo ogukuŋŋaanyizibwa, emmere gye balya, n’okugejja. Kino kiraga nti Ipa eyinza okuba n’omulimu ogumu mu kulongoosa enkola y’olubuto era eyinza okuyamba okulongoosa enkola y’okugaaya emmere n’okunyiga mu balwadde abalina obuzibu bw’obusimu bw’okukula. [4] ..
Mu bufunze, nga ekitumbula okufulumya obusimu bw’okukula obulonda, Ipa esitula bulungi okufulumya obusimu bw’okukula ng’ekola ekirungo ekifulumya obusimu bw’okukula ekya peptide receptor (GHS receptor), awatali kukosa nnyo miwendo gya adrenocorticotropic hormone (ACTH) ne cortisol. Emirimu gyayo mulimu okutumbula okufulumya obusimu obukula, okulung’amya entambula y’olubuto n’okukendeeza ku bulumi. Okulonda kwayo okw’amaanyi n’engeri z’ebigendererwa bingi biwa obusobozi bw’okukozesa mu bujjanjabi, ekigifuula esaanira okukozesebwa mu mbeera ng’obutaba na busimu bw’okukula, okuzibikira kw’ekyenda oluvannyuma lw’okulongoosebwa, n’okuddukanya obulumi.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Raun K munoonyereza akwatagana ne Technical University of Denmark (DTU) ne Novo Nordisk Foundation. Okunoonyereza kwe kukwata ku bintu ebitali bimu, omuli Endocrinology & Metabolism, Orthopaedics, Nutrition & Dietetics, Veterinary Sciences, neEngineering. Omulimu gwe gutera okussa essira ku kukulaakulanya eby’okugonjoola ebizibu ebiwangaala era ebiyiiya naddala mu mbeera ya tekinologiya w’ebiramu n’ebyenfuna ebisinziira ku biramu.
Raun K abaddeko mu pulojekiti ezikwata ku Novo Nordisk Foundation Center for Biosustainability ku DTU, eyeewaddeyo okutumbula dizayini y’amakolero g’obutoffaali, yinginiya w’enkyukakyuka y’emmere, n’ebiramu eby’obutonde okusobola okukola ebiramu mu ngeri ey’omulembe. Okugatta ku ekyo, abadde yeenyigira mu nteekateeka z’okunoonyereza ezigendereddwamu okukendeeza okwesigama ku bintu ebiva mu bifo eby’edda n’okutumbula enkyukakyuka za kiragala ng’ayita mu bikozesebwa mu kukola ebiramu.
Omulimu gwe era gukwata ku nkola ya yinginiya, gamba ng’okukola ebirungo ebiziyiza (catalysts) n’ebikozesebwa mu bulamu (bioprocesses) okusobola okuyimirizaawo amakolero n’obutonde bw’ensi. Enkola ya Raun K ey’okugatta eby’emikono ekwataganya okunoonyereza kwa ssaayansi n’okukozesebwa mu nkola, n’ekola kinene mu by’ensoma n’amakolero. Raun K awandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [3].
