I-insulin umuthi ophambili wokwelapha isifo sikashukela sohlobo 1. Kwesinye isikhathi sisetshenziselwa ukuqinisa isimo sesiguli futhi sithuthukise inhlala-kahle yakhe kuhlobo lwesibili lwesifo. Le nto ngokwemvelo yayo i-hormone ekwazi ukuthonya amandla ama-carbohydrate emithanjeni emincane. Imvamisa, amanyikwe akhiqiza i-insulin eyanele, esiza ukugcina izinga lokudla ushukela egazini. Kepha uma unezifo ezibucayi ze-endocrine, okuwukuphela kwendawo yokusiza isiguli imijovo ye-insulin. Ngeshwa, akunakwenzeka ukuyithatha ngomlomo (ngesimo samathebulethi), ngoba ichithwa ngokuphelele emgodini wokugaya ukudla futhi ilahlekelwe inani layo lezinto eziphilayo.
Izinketho zokuthola i-insulin ukuze uzisebenzise kwezokwelapha
Abaningi besifo sikashukela okungenani bake bazibuza ukuthi ngabe i-insulin, esetshenziselwa ukwelashwa yenziwe ini. Okwamanje, kaningi lo muthi utholakala kusetshenziswa izindlela zobunjiniyela bezakhi zofuzo kanye ne-biotechnology, kepha kwesinye isikhathi kukhishwa ezintweni ezingavuthiwe zomsuka wesilwane.
Amalungiselelo atholakala ezintweni zokusetshenziswa kwezilwane ezivela emvelweni
Ukuthola le hormone kusuka kumanyikwe ezingulube nasezinkomeni kungubuchwepheshe obudala obusetshenziswa kakhulu namuhla. Lokhu kungenxa yekhwalithi ephansi yesidakamizwa, ukuthambekela kwayo okubangela ukungahambi kahle komzimba kanye nokuhlanzwa okunganele. Iqiniso ngukuthi njengoba i-hormone iyi-protein, iqukethe isethi ethile yama-amino acid.
Ekuqaleni kanye maphakathi nekhulu lama-20, lapho izidakamizwa ezifanayo zazingekho, ngisho ne-insulin enjalo kwakuyimpumelelo kwezokwelapha futhi yavumela ukuthatha ukwelashwa kwabanesifo sikashukela kufinyelele ezingeni elisha. Ama-hormone atholakala ngale ndlela anciphisa ushukela wegazi, noma kunjalo, ayevame ukubanga imiphumela emibi nokwaliwa yilesi sifo. Ukwehluka ekwakhiweni kwama-amino acid nokungcola emthini kuthinte isimo seziguli, ikakhulukazi ezigabeni ezisengozini kakhulu yeziguli (izingane kanye nabantu asebekhulile). Esinye isizathu sokungabekezeleleki kabi kwe-insulin okunjalo ukuba khona kwangaphambi kwayo kokungasebenzi komuthi (i-proinsulin), obekungenakwenzeka ukuqeda kulokhu kuhluka kwezidakamizwa.
Kulezi zinsuku, kukhona ama-insulin angaphambili athuthukile angenawo la maphutha. Zitholakala kuma-pancreas engulube, kepha ngemuva kwalokho afakwa ekucutshungweni nasekuhlanzweni okwengeziwe. Zinezinto ezixubile futhi ziqukethe okutholwe kuzo.
I-insulin yengulube eshintshiwe ayifani ne-hormone yomuntu, ngakho-ke isasetshenziswa ekuzijwayeza
Le mishanguzo ibekezelelwa yiziguli kangcono kakhulu futhi empeleni azibangeli ukusabela okungekuhle, azivimbeli amasosha omzimba futhi zinciphise ushukela wegazi ngempumelelo. I-Bovine insulin ayisetshenziswa kwezokwelapha namuhla, ngoba ngenxa yesakhiwo sayo sangaphandle ithinta kabi amasosha omzimba nezinye izinhlelo zomzimba womuntu.
I-Insulin Engineering Insulin
I-insulin yomuntu, esetshenziselwa abanesifo sikashukela, ngokwezimboni itholakala ngezindlela ezimbili:
Izimo zokugcina i-insulin- usebenzisa ukwelashwa kwe-enzymatic ye-porcine insulin;
- kusetshenziswa izinhlobo zemvelo eziguqulwe ngofuzo zika-E. coli noma imvubelo.
Ngokushintshwa kwamakhemikhali e-physico-chemicals, ama-molecule we-porcine insulin ngaphansi kwesenzo sama-enzymes akhethekile afana ne-insulin yomuntu. Ukwakhiwa kwe-amino acid kokulungiselela okuhlukile akufani nokwakheka kwe-hormone yemvelo ekhiqizwa emzimbeni womuntu. Ngesikhathi senqubo yokukhiqiza, umuthi uthola ukuhlanzwa okuphezulu, ngakho-ke, akubangeli ukusabela komzimba noma okunye ukubonakaliswa okungathandeki.
Kepha imvamisa, i-insulin itholakala kusetshenziswa ama-microorganisms aguquliwe (genetically modified). Besebenzisa izindlela ze-biotechnological, amagciwane noma imvubelo iguqulwa ngendlela yokuthi yona uqobo ingakhiqiza i-insulin.
Kunezindlela ezi-2 zokukhiqizwa kwe-insulin okunjalo. Eyokuqala yazo isuselwa ekusetshenzisweni kwezinhlobo ezimbili (izinhlobo) ezihlukile ze-microorganism eyodwa. Ngasinye sazo sakha iketane elilodwa le-molecule ye-DNA (kukhona amabili kuphela, futhi asontekile ndawonye). Ngemuva kwalokho la maketane axhumekile, futhi kwisixazululo esivele sikhona kungenzeka ukuthi ahlukanise izinhlobo ezisebenzayo ze-insulin kulawo angathwali ukubaluleka kokuzala.
Indlela yesibili yokuthola umuthi usebenzisa i-Escherichia coli noma imvubelo kusekelwe ekutheni i-microbe kuqala ikhiqiza i-insulin engasebenzi (okungukuthi, owandulelayo wayo, i-proinsulin). Ngemuva kwalokho, kusetshenziswa ukwelashwa kwe-enzymatic, leli fomu liyasebenza futhi lisetshenziswe kwezokwelapha.
Abasebenzi abathola izisetshenziswa ezithile zokukhiqiza kumele bahlale begqoke isudi yokuvikela oyinyumba, eqeda ukuxhumana nomuthi ngezinsizi zabantu zebhayoloji.
Zonke lezi zinqubo zivame ukuzenzakalela, umoya futhi yonke indawo ebonakalayo ihlangana nama-ampoules kanye nezimbiza iyinyumba, futhi imigqa enezinto zokusebenza ivaliwe ngendlela engenamkhawulo.
Izindlela ze-biotechnology zenza ososayensi bakwazi ukucabanga ngezinye izixazululo zesifo sikashukela. Isibonelo, kuze kube manje, kwenziwa ucwaningo olwenziwa ngaphambi kokukhiqizwa kwamaseli we-beta okwenziwe nge-pancreas, angatholakala ngokusebenzisa izindlela zobunjiniyela bezakhi zofuzo. Mhlawumbe ngokuzayo zizosetshenziselwa ukwenza ngcono ukusebenza kwalesi sitho kumuntu ogulayo.
Ukukhiqizwa kwamalungiselelo we-insulin anamuhla inqubo eyinkimbinkimbi yezobuchwepheshe ebandakanya ukuzenzakalelayo nokungenelela okuncane komuntu
Izinto ezengeziwe
Ukukhiqizwa kwe-insulin ngaphandle kwabafakeli ezweni lanamuhla cishe akunakucabanga, ngoba bangathuthukisa izakhiwo zayo zamakhemikhali, bandise isikhathi sokwenza okuthile futhi bazuze ukuhlanzeka okuphezulu.
Ngezakhiwo zabo, zonke izithako ezingeziwe zingahlukaniswa ngezigaba ezilandelayo:
- izandiso (izinto ezisetshenziselwa ukuhlinzeka isikhathi eside somuthi);
- izinto ezibulala amagciwane;
- abaqinisi, ngenxa yokuthi i-acidity efanele igcinwa endaweni yesisombululo somuthi.
Ukunwebisa Izithasiselo
Kukhona ama-insulin asebenza isikhathi eside omsebenzi wawo wezinto eziphilayo uhlala amahora angama-8 kuye kwangama-42 (kuya ngeqembu lesidakamizwa). Lo mphumela utholakala ngenxa yokufakelwa kwezinto ezikhethekile - izandiso enkingeni yomjovo. Ngokuvamile, enye yalezi zingxube ezilandelayo isetshenziselwa le nhloso:
- amaprotheni;
- usawoti we-chloride we-zinc.
Amaprotheni akhulisa isenzo somuthi uthola ukuhlanzwa okuningiliziwe futhi ane-allergenic (isb. Protamine). Usawoti we-Zinc nawo awuthinti kabi umsebenzi we-insulin noma inhlala-kahle yabantu.
Izindawo zokwenzelela
Izinto zokuhlanza ukwakheka kwe-insulin ziyadingeka ukuze izitshalo ezincane ezingamaphiko zingaphindaphindeki ngesikhathi sokugcinwa nokusetshenziswa kukho. Lezi zinto ziyizigcinamthetho futhi ziqinisekisa ukugcinwa komsebenzi wezinto eziphilayo lomuthi. Ngaphezu kwalokho, uma isiguli siphatha i-hormone kusuka ku-vial eyodwa kuye kuphela, khona-ke umuthi ungahlala izinsuku eziningana. Ngenxa yezakhi ezisezingeni eliphakeme ze-antibacterial, ngeke abe nesidingo sokulahla umuthi ongasetshenzisiwe ngenxa yokuthi kungenzeka ukuthi kungenzeka ukuthi uphinde uzalwe kabusha kusisombululo samagciwane.
Izinto ezilandelayo zingasetshenziswa njengezibulala magciwane ekwakhiweni kwe-insulin:
- metacresol;
- phenol;
- parabens.
Uma isixazululo siqukethe ama-zinc ion, nawo asebenza njengesibambiso esingeziwe ngenxa yezakhiwo zawo zokulwa nazo
Izakhi ezithile zokubulala amagciwane zilungele ukukhiqizwa kohlobo ngalunye lwe-insulin. Ukuxhumana kwabo ne-hormone kumele kuphenywe esigabeni sokuhlolwa kwangaphambi kokugcina, ngoba lokhu okugcinwe kungafanele kungaphuli umsebenzi we-insulin noma kungenjalo kuthinte izakhiwo zawo ngendlela engeyiyo.
Ukusetshenziswa kwezivikelo ezimweni eziningi kuvumela ukuthi i-hormone iphathwe ngaphansi kwesikhumba ngaphandle kokwelashwa kwangaphambili ngotshwala noma ngamanye ama-antiseptics (umenzi uvame ukubhekisa kulokhu emiyalweni). Lokhu kwenza ukuphathwa kwezidakamizwa kube lula futhi kunciphise inani lokukhwabanisa lokulungiselela ngaphambi komjovo uqobo. Kepha lokhu kuncoma kusebenza kuphela uma isisombululo sifakwe nge-insulin eyodwa yenaliti nenaliti emincane.
Abaqinisi
Ama-solidabilizer ayadingeka ukuze i-pH yesisombululo igcinwe ezingeni elinikeziwe. Ukugcinwa komuthi, umsebenzi wawo kanye nokuqina kwezakhiwo zamakhemikhali kuncike kuzinga le-acidity. Ekwenziweni kwe-hormone ejova yeziguli ezinesifo sikashukela, ama-phosphates ajwayele ukusetshenziselwa le njongo.
Nge-insulin ene-zinc, izixazululo zokuqina azidingi njalo, ngoba ama-ion wensimbi asiza ukugcina ibhalansi edingekayo. Uma zisetshenziswa noma kunjalo, ezinye izinhlanganisela zamakhemikhali zisetshenziswa esikhundleni se-phosphates, ngoba ukuhlanganiswa kwalezi zinto kuholela ekushwabeni kanye nasekungafanelekeni komuthi. Impahla ebalulekile eboniswe kubo bonke abaqinisi ukuphepha kanye nokungakwazi ukungena kunoma yikuphi ukuvela nge-insulin.
I-endocrinologist efanelekayo kufanele ibhekane nokukhethwa kwezidakamizwa zokujova zesifo sikashukela ngasinye. Umsebenzi we-insulin akuyona nje ukugcina izinga elijwayelekile loshukela egazini, kodwa futhi hhayi ukulimaza ezinye izitho nezinhlelo. Umuthi kufanele ungathathi hlanganiso ngamakhemikhali, ungabi nampilo futhi ungabizi kakhulu. Futhi kulula impela uma i-insulin ekhethiwe ingahlanganiswa nezinye izinguqulo zayo ngokuya ngesikhathi sokwenza okuthile.
