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▎ IGF-1 LR3 kye ki?
IGF-1 LR3 ye analog ekola okumala ebbanga eddene eya insulin-like growth factor 1 (IGF-1). Okuyita mu kukyusa ensengekera, asidi wa glutamic mu kifo 3 akyusibwamu arginine, nga waliwo amino asidi endala 13 ku N-terminus, ne zikola molekyu ekola eya amino asidi 83. Bw’ogeraageranya ne IGF-1 ey’obutonde (amino acids 70), ekitundu ky’obulamu bwayo kiwanvuwa okutuuka ku ssaawa 20-30 ng’amaanyi geeyongedde emirundi nga esatu. Kikwatagana bunafu ku puloteyina ezisiba IGF, kisiba nnyo ku kikwata kya IGF-1, era kikola amakubo ga PI3K/Akt ne MAPK.
▎ ya IGF-1 LR3 Enzimba
Ensibuko: PubChem |
Mu nsonga : CRZOPHSORDIMRX-UHFFFAOYSA-N Ensengekera ya molekyu: C 80H 154N 4O 6S2 Obuzito bwa molekyu: 1332.2 g/mol Ennamba ya CAS: 946870-92-4 Ekitongole kya PubChem CID:168009904 |
▎ IGF-1 LR3 Okunoonyereza ku
Kiki ekiva mu kunoonyereza ku IGF-1 LR3?
Okunoonyereza ku IGF-1 LR3 kwasibuka mu bwetaavu bw’okuvvuunuka obuzibu bw’ensonga y’okukula ey’obutonde eringa insulini 1 (IGF-1). Nga omulungamya omukulu ow’okukula kw’obutoffaali, okwawukana, n’okukyusakyusa mu mubiri, IGF-1 ey’obutonde eraga obusobozi mu kuddaabiriza ebitundu, okunoonyereza ku kukula n’enkulaakulana, n’okuyingira mu nsonga z’endwadde. Wabula erina ebizibu ebinene: Ekitundu ky’obulamu bwayo bumala essaawa ntono zokka, ekivaako okulongoosebwa amangu mu vivo. Ekirala, yeekwata nnyo ku puloteyina ezisiba IGF, ekivaamu ekitundu ekitono eky’ebika eby’eddembe, ebikola ebilwana okukola ebikolwa ebiwangaala. Ebizibu bino byaziyiza nnyo obulungi bwayo mu kunoonyereza okw’okugezesa n’okukozesebwa okuyinza okubaawo, ekyaleetera bannassaayansi okunoonyereza ku analogues ezikyusiddwa mu nsengeka nga zirina omulimu ogwongezeddwa.
Olw’enkulaakulana mu by’obulamu bwa molekyu ne tekinologiya wa yinginiya wa puloteyina, ttiimu z’abanoonyereza zaassa essira ku kukyusa ddala IGF-1 okulongoosa eby’obugagga byayo. Okuyita mu kunoonyereza okw’obwegendereza ku nkolagana y’ensengekera n’emirimu gya IGF-1, abanoonyereza baakizuula nti enkyukakyuka mu bifo ebitongole ebikola amino asidi zisobola okukwata ku nkolagana yaayo ne puloteyina ezisiba n’ebikwata: Okukyusa asidi wa glutamic mu kifo 3 ne arginine n’okugattako amino asidi 13 ku N-terminus kikendeeza ku nkolagana yaayo ne puloteyina esiba IGF, ne kikendeeza ku ngeri ezisiba ezitakola ate nga kyongera ku kusiba okutuuka ku kirungo ekikwata IGF-1. Mu kiseera kye kimu, okulongoosa enzimba yagaziya enzirukanya y’enkyukakyuka ya molekyu mu vivo, okukkakkana nga kivaamu IGF-1 LR3 ne amino asidi 83. Kino kyavaamu ekitundu ky’obulamu okuwanvuwa okutuuka ku ssaawa 20-30 ate nga n’amaanyi geeyongera emirundi nga esatu.
Enkola y’okukola kwa IGF-1 LR3 eri etya?
Okweyongera kw’obutoffaali n’okwawukana
Okusikirizibwa kw’okukula kw’ebinywa by’amagumba: Mu kiseera ky’okukula kw’omwana ali mu lubuto, IGF-1 LR3 etumbula nnyo okukula kw’ebinywa by’amagumba ebiyitibwa myoblasts. Okugeza, okunoonyereza ku baana b’endiga abalwawo olubuto kwalaga nti oluvannyuma lwa wiiki emu nga bafuyiddwa IGF-1 LR3, emiwendo gy’okukula kw’ebinywa by’amagumba gyeyongera nnyo (P < 0.05). Kino kiraga nti IGF-1 LR3 ekola butereevu ku myoblasts okutumbula enzirukanya y’obutoffaali, okusobozesa myoblasts eziwera okuyingira mu mbeera y’okukula era bwe kityo n’ewa ensibuko z’obutoffaali endala ez’okukula n’okukula kw’ebitundu by’ebinywa [1]..
Okukwata ku nkula y’enkwaso: Mu kiseera ky’enkola y’enkwaso, IGF-1 LR3 yeetaba mu kulungamya okukula n’enkula y’enkwaso. Mu nkola ya rat superovulation model, okukozesa awamu IGF-1 LR3 ne gonadotropins kyayongera okwongera ku miwendo gy’okuggyamu enkwaso n’okulinnyisa obuzito bw’enkwaso mu bika by’envunza ebimu. Kino kiraga nti IGF-1 LR3 eyinza okukosa okukula kw’enkwaso n’okufulumya eggi ng’etereeza okukula n’okwawukana kw’obutoffaali bwa granulosa, bwe kityo n’ekosa enkola y’okuzaala [2]..
Okulungamya Enkyukakyuka y’Emirundi
Okufuna n’okukozesa ebiriisa: Oluvannyuma lw’okufukibwa IGF-1 LR3 mu baana b’endiga abamaze olubuto, okukendeera kw’emiwendo gy’okuyingiza amino asidi mu nnabaana kwalabiddwa wamu n’obungi bwa amino asidi mu lubuto obutono, wadde nga emiwendo gya puloteyina y’omwana mu lubuto egy’okukyusakyusa egy’enjawulo. Kino kiraga nti IGF-1 LR3 eyinza okukosa enkola y’okutwala ebiriisa mu lubuto n’okukozesa, okusobozesa okukozesa obulungi ebiriisa ebitono okuwagira okukula kw’ebitundu by’omubiri okusinga okwongera ku kugaba ebiriisa mu lubuto okuyita mu kutambula kw’omusaayi mu nnabaana oba okusikirizibwa okutambuza ebiriisa [2]..

Ekifaananyi 1 IGF-1 eziyiza okuzimba era eyanguya okukola emisuwa ng’eyita mu makubo g’obubonero bwa Ras/PI3K/IKK/NF-κB okutumbula okuwona kw’ebiwundu [3]..
Okuziyiza Okufulumya Insulini: Okufuyira IGF-1 LR3 oba omunnyo mu baana b’endiga abazaalibwa mu lubuto ekikeerezi kyalaga nti insulini mu plasma yakendedde mu baana b’endiga abafukiddwa IGF-1 LR3. Okugatta ku ekyo, okufulumya insulini mu kiseera ky’okugezesa kwa hyperglycemic clamp kwakendeera bw’ogeraageranya n’abafuga. Kino kiraga nti IGF-1 LR3 eyinza okukola butereevu ku butoffaali bwa β obw’olubuto okuziyiza okufulumya insulini. Okunoonyereza okulala ku bizinga by’omwana ali mu lubuto ebyawuddwamu kwalaga nti ebizinga okuva mu baana b’endiga abafukiddwa IGF-1 LR3 byalaga okufulumya insulini okutono obutasalako mu kuddamu okusikirizibwa kwa glucose mu vitro, ekiraga nti IGF-1 LR3 eyinza okuleeta obulema obw’omunda mu butoffaali bwa β obw’olubuto, okukosa enkola ya bulijjo ey’okufulumya insulini [4,5].
Okulungamya enkola y’okutondebwa kw’emisuwa
Omulimu mu kukola emisuwa gy’enkwaso: Mu kugezesa obuwangwa bw’okuzaala emisuwa gy’ente eziriko luteinized follicle, ebikolwa bya IGF-1 LR3 ku mikutu gya luteinized follicle endothelial cell (EC) n’okukola progesterone byanoonyezebwa. Ebivuddemu biraga nti waliwo akakwate akatono ku bipimo by’okukula kwa EC naye okweyongera okutono mu kweyongera kw’obutoffaali (3–5%). Okwawukana ku ekyo, IGF-1 LR3 yakola ebikolwa eby’enjawulo ku kukola progesterone, so nga IGF-1 receptor antagonist picropodophyllin (PPP) yakendeeza nnyo ku byombi EC growth parameters n’obungi bwa progesterone. Kino kiraga nti IGF-1 LR3 eyinza okukyusakyusa okukola emisuwa n’okukola progesterone mu luteinized follicles okuyita mu IGF-1 receptor signaling pathway, bwe kityo n’ekuuma enkola y’enkwaso n’okuzaala [6]..
Ebikozesebwa bya IGF-1 LR3 bye biruwa?
Okunoonyereza ku nkula n’enkulaakulana y’ebisolo n’okubikozesa
Okutumbula okukula kw’ebitundu by’omubiri gw’omwana mu lubuto: Mu kugezesa ku baana b’endiga abamaze olubuto, okufuyira IGF-1 LR3 kyayongera nnyo okukula kw’ebitundu by’omwana mu lubuto, ne kitumbula enkula y’ebitundu by’omubiri ng’omutima, ensigo, enseke, n’endwadde z’ekibumba. Kino kiraga nti IGF-1 LR3 ekola kinene nnyo mu kulungamya enkola z’enkula y’ebitundu by’omubiri gw’omwana mu lubuto, ekiyamba okutegeera ennyo enkola z’okulungamya enkula n’enkula y’omwana mu lubuto. Ewa obuwagizi obw’enzikiriziganya n’obulagirizi obw’omugaso okutumbula enkola y’okuzaala kw’ebisolo n’okutumbula emiwendo gy’abaana abawangaala [1]..
Okusitula okukula kw’ebinywa by’amagumba: Okunoonyereza kulaga nti IGF-1 LR3 esitula okukula kw’ebinywa by’amagumba. Mu kugezesa endiga ezizaalibwa mu lubuto, IGF-1 LR3 infusion markedly enhanced myoblast proliferation activity [1]..
Okunoonyereza ku ssukaali n’endwadde ezikwatagana nabyo
Okukebera ebikosa ku kufulumya insulini: Okugezesa okwalimu okufuyira IGF-1 LR3 mu baana b’endiga abazaalibwa mu lubuto kwalaga okukendeera mu bungi bwa insulini mu plasma y’omwana mu lubuto. Mu kugezesa kwa hyperglycemic clamp, emiwendo gya insulin mu baana b’endiga abazaalibwa nga bajjanjabiddwa IGF-1 LR3 gyali wansi ebitundu 66% okusinga mu bafuga. Ekintu kino kiraga akakwate akayinza okubaawo wakati wa IGF-1 LR3 n’okufulumya insulini, nga kiwa obubonero obukulu okunoonyereza ku ntandikwa y’obulwadde bwa sukaali n’okukola enkola empya ez’obujjanjabi [5]..
Enkolagana n’omutindo gw’emizannyo: Okunoonyereza ku baddusi n’abawuzi abakulu mu Yisirayiri kwalaga nti enkyukakyuka z’obuzaale bwa IGF1 zikwatagana n’emiwendo gya IGF1 egy’okutambula, era nti obubonero bw’obuzaale bwa IGF (IGF-GS) bw’abaddusi bukwatagana n’omutindo gw’emizannyo. Abaddusi ab’ekika ekya waggulu baayolesa obubonero bwa IGF-GS obwa wakati okusinga abaddusi ab’omutindo gw’eggwanga n’abawuzi ab’ebanga ettono ab’omutindo ogwa waggulu. Kino kiraga nti enkola ya IGF-1 eyinza okukola kinene mu mizannyo gy’oku sipiidi egy’oku ttaka. Wadde nga tekikakasibwa oba IGF-GS esobola okukozesebwa okulonda abaddusi ab’ekika ekya waggulu nga bukyali, etuwa emitendera emipya egy’okulonda bannabyamizannyo n’okuyingira mu nsonga z’okutendekebwa. Okunoonyereza mu biseera eby’omu maaso kuyinza okusobozesa okukola enteekateeka z’okutendekebwa ezisinga okugendereddwamu okutumbula omutindo gw’emizannyo nga balondoola n’okwekenneenya obubonero obukwatagana ne IGF-1 mu bannabyamizannyo [7]..
Okunoonyereza mu biology y’obutoffaali n’obusawo obusookerwako
Okunoonyereza ku kulungamya okukula kw’obutoffaali: IGF-1 LR3 erina obusobozi okusitula okukula kw’obutoffaali. Okugezesa mu vitro kulaga okusitula kwayo okulungi okw’okukula kw’obutoffaali bwa NIH 3T3. Kino kifuula IGF-1 LR3 ekintu eky’omuwendo mu kunoonyereza ku nkola z’okulungamya okukula kw’obutoffaali. Nga twetegereza ebikolwa bya IGF-1 LR3 ku kweyongera mu layini z’obutoffaali ez’enjawulo, abanoonyereza basobola okufuna amagezi ku nkola z’ebiramu ezikulu nga okulungamya enzirukanya y’obutoffaali n’amakubo g’obubonero, okuwa omusingi gw’enzikiriziganya ogw’okunoonyereza mu bulwadde bwa kkansa, eddagala erizza obuggya, n’ebintu ebikwatagana nabyo [8]..
Apoptosis and Protein Metabolism Research: Mu kunoonyereza ku butoffaali bwa C2C12 obujjanjabiddwa haidrojeni perokisayidi, IGF-1 (nga mw’otwalidde ne analog IGF-1 LR3 yaayo) ekyusa enkola y’okusengejja obutoffaali bw’obutoffaali n’okuvunda nga etereeza Pax7, ensonga ezifuga myogenic (MRFs), mTOR, ne P70S6K, okukendeeza MuRF1 ne MAFbx, n’okuziyiza apoptosis, bwe kityo ne kitereeza bbalansi wakati w’okusengejja puloteyina n’okuvunda. Kino kiyamba okutegeera ennyo enkola z’obulamu n’okufa kw’obutoffaali wansi w’embeera z’okunyigirizibwa, awamu n’emikutu gy’okulungamya enkyukakyuka ya puloteyina, nga giwa ebigendererwa ebipya n’okutegeera okujjanjaba endwadde ezikwatagana [9]..
Mu bufunzi
IGF-1 LR3, nga synthetic long-acting analog of insulin-like growth factor 1, etumbula okukula kw’ebitundu by’omubiri mu mutima gw’omwana ali mu lubuto n’endwadde z’ekibumba nga ekola amakubo g’obubonero nga PI3K/Akt ne MAPK. Kisitula okukula kw’ebinywa by’amagumba n’okukola puloteyina, kitereeza enkyukakyuka mu mubiri, kikuuma obulamu bw’ebinywa by’amagumba, era kiyamba okuwona obuvune obuva ku dduyiro.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Feng L munoonyereza ng’essira aliteeka ku mulimu gw’okukola dduyiro n’obulamu bw’emisuwa. Omulimu gwabwe ogw’okusoma okusinga gwesigamye ku kunoonyereza ku bikolwa eby’okulungamya eby’engeri ez’enjawulo ez’okukola dduyiro ku mirimu gy’omubiri naddala enkolagana wakati wa dduyiro n’enkola za molekyu z’omubiri ezikwata ku bulamu bw’ebinywa n’okuwona endwadde z’emisuwa. Dr. Feng atera okwettanira enkola y’okunoonyereza nga tekunnabaawo n’obukodyo bw’okunoonyereza ku molekyu okukola okunoonyereza okw’obwegendereza. Feng L ewandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [9].
▎ Ebiwandiiko Ebikwatagana
[1] Stremming J, White A, Donthi A, n’abalala. Sheep recombinant IGF-1 etumbula okukula kw’ebitundu by’omubiri mu ndiga ezizaalibwa mu lubuto. Ensalo mu by’omubiri 2022; 13: 954948.DOI: 10.3389/fphys.2022.954948.
[2] Khamsi F, Roberge S, Wong J. Okwolesebwa okupya okw’omulimu gw’omubiri/eddagala ogw’ensonga y’okukula eringa insulini-1 mu kuggyamu eggi mu nvunza n’okukola ku cumulus oophorus. Endocrine 2001 mu bitundu by’omubiri; 14(2): 175-180.DOI: 10.1385/ENDO:14:2:175.
[3] Zhang X, Hu F, Li J, n’abalala. IGF-1 eziyiza okuzimba era eyanguya okukola emisuwa ng’eyita mu makubo g’obubonero bwa Ras/PI3K/IKK/NF-κB okutumbula okuwona kw’ebiwundu. European Journal of Sayansi w’Eddagala 2024; 200: 106847.DOI: 10.1016/j.ejps.2024.106847.
[4] White A, Stremming J, Boehmer BH, n’abalala. Okukendeera kw’okufulumya insulini esikirizibwa glucose oluvannyuma lw’okufukibwa IGF-1 okumala wiiki emu mu ndiga ezirina olubuto olusembayo kiva ku buzibu bw’ekizinga obw’omunda. American Journal of Physiology-Endocrinology n’enkyukakyuka mu mubiri 2021; 320(6): E1138-E1147. DOI:10.1152/ajpendo.00623.2020.
[5] White A, Stremming J, Brown L. D., Rozance P. J., ne bannaabwe abalala. Okukendeeza ku kufulumya insulini okusikirizibwa glucose mu kiseera ky’okufuyira IGF-1 LR3 okw’amangu mu ndiga ezizaalibwa mu lubuto tekusigala mu bizinga ebyawuddwamu. Journal of Enkulaakulana y’Ensibuko y’Ebyobulamu n’Endwadde 2023; 14(3): 353-361.DOI: 10.1017/S2040 17442300009 0. Enkola y’okukuuma obutonde bw’ensi.
[6] Nwachukwu C. U., Robinson R. S., Woad K. J., ne bannaabwe abalala. Enkola y’enkola y’ensonga y’okukula eringa insulini ku luteinising angiogenesis. Okuzaala n’okuzaala 2023; 4(2).DOI: 10.1530/RAF-22-0057.
[7] Ben-Zaken S, Meckel Y, Nemet D, Eliakim A. Obubonero bw’obuzaale bw’ensonga y’okukula eringa insulini. Journal of Okunoonyereza ku maanyi n’okutereeza embeera 2021; 35(9): 2421-2426.DOI: 10.1519/JSC.000000000000000004102.
[8] Mao W. Okwolesebwa okw’omutindo ogwa waggulu okw’olujegere oluwanvu Arg ~ 3-IGF-1 mu Pichia pastoris n’okulongoosebwa kwayo n’okulaga obubonero bwayo. Bulletin y’ekitongole kya ssaayansi w’obusawo mu by’amagye 2008. https://api.semanticscholar.org/CorpusID:88212024.
[9] Feng L, Li B, Xi Y, Cai M, Tian Z. Dduyiro ow’omukka n’okukola dduyiro w’okuziyiza bikendeeza ku kukendeera kw’ebinywa by’amagumba okuyita mu kkubo lya IGF-1/IGF-1R-PI3K/Akt mu mbeba ezirina okuzimba emisuwa gy’omutima. American Journal of Physiology-Ebyobulamu by’obutoffaali 2022; 322(2): C164-C176.DOI: 10.1152/ajpcell.00344.2021.
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.