Methylene blue na diyabete: gusobanura itwarwa rya glikoze n'ubushakashatsi ku nyamaswa

Ikibazo cyihishe inyuma y'amagambo yo kuyamamaza

Uwo mwanzuro usa n'uwumvikana, ariko ushingiye ku buryo butari bwo bwo kubyumva. Ufata ibintu bitatu bitandukanye nk'aho ari kimwe: glikoze yinjira mu karemangingo kamwe kari mu gikoresho cya laboratwari, ihinduramatwara ribera muri mitokondiriya y'umutima, n'igenzura rya glikoze mu muntu wese. Buri kimwe gifite ibipimo byacyo n'aho ubushobozi bwacyo bugarukira. Iyi nkuru ibitandukanya.

Igisubizo kigufi: methylene blue koko ikangura itwarwa rya glikoze mu bwoko bumwe bw'uturemangingo bwakozweho ubushakashatsi bwinshi, kandi koko ihindura imikorere ya shimi muri mitokondiriya n'ibipimo bimwe by'umutima mu mbeba zirwaye diyabete. Ariko mu bushakashatsi ku mbeba bwamaze igihe kirekire kurusha ubundi, ntiyahinduye glikoze ipimwa umuntu atariye cyangwa hemoglobine ifatanye na glikoze, kandi nta bimenyetso byatangajwe ku bantu byerekana ko methylene blue ikoreshwa ikagera mu mubiri wose ituma isukari yo mu maraso, HbA1c cyangwa insuline birushaho kugenzurwa neza muri diyabete.

Uturemangingo: glikoze yinjira vuba iciye mu poroteyine ziyitwara zisanzwe mu gihu cy'akaremangingo

Abashakashatsi bakoresheje uturemangingo twa fibroblast twa L929, ubwoko bw'uturemangingo iyinjira rya glikoze ryabwo rishingiye kuri poroteyine imwe iyitwara, GLUT1. Kubera ko harimo poroteyine imwe gusa iyitwara, impinduka iyo ari yo yose mu iyinjira rya glikoze igomba guturuka kuri iyo poroteyine.

Igihe itsinda ryashyiraga methylene blue kuri utu turemangingo, iyinjira rya glikoze yashyizweho ikimenyetso cyo kuyikurikirana ryiyongereye mu minota 10 kandi rikiyongera uko ingano ya methylene blue yiyongeraga, rigera hafi kuri 800 ku ijana by'urwego rw'ibanze kuri 50 micromolar mu minota 45. Ibisobanuro by'umuvuduko w'itwarwa ni ingenzi: umuvuduko ntarengwa (Vmax) wariyongereye, mu gihe ubushobozi bwo gufata glikoze (Km) n'ingano ya poroteyine ya GLUT1 bitahindutse. Umubare umwe w'amarembo watumye glikoze nyinshi kurushaho inyuramo buri munota. Iri rangi ryakanguye poroteyine zitwara glikoze zisanzwe mu gihu cy'akaremangingo aho kongeramo izindi nshya.

Igerageza ryo kugenzura ibyavuye mu bushakashatsi rituma birushaho gusobanuka. Uburyo bw'iri rangi bwakiriye electron, butagira ibara, nta cyo bwakoze. Ikintu gitera okisidasiyo cyari hanze y'akaremangingo kandi cyabuzaga irangi kwinjira cyahagaritse haba gufata ibara cyangwa gukangurwa kw'itwarwa. Ibibuza inzira za AMP kinase na PI kinase nta cyo byahinduye, ibyo bikaba bidashyigikira ko izo nzira ebyiri zizwi zo gutanga ibimenyetso ari zo zibigiramo uruhare.

Igitekerezo cya mbere cyari uruzenguruko rwa redox: irangi ritwara electron, rigashyira akaremangingo mu ihungabana rito, maze uturemangingo twahungabanye tugafungura amarembo ya glikoze. Ubushakashatsi bwakurikiyeho bwagerageje icyo gitekerezo. Abashakashatsi bakoresheje methyl-beta-cyclodextrin, molekile imeze nk'impeta ifungirana methylene blue mu ihuriro riyikubiyemo (igipimo gihoraho cy'ihuzwa kiri hafi ya 310 M-1). Irangi ryafungiraniwe ntiryasize uturemangingo ibara kandi ntiryakanguye iyinjira rya glikoze; uko irangi ryakurwagamo hakoreshejwe kwoza, ni ko ingaruka yaryo yagabanukaga. Umwanzuro wabo wahabanye n'igisobanuro cya redox: gukangurwa bishobora kuba bituruka ku mikoranire itaziguye y'irangi na poroteyine imwe iri mu nzira yo gukangura GLUT1, aho guturuka ku ihungabana rusange riterwa na okisidasiyo.

Ihame ry'imikorere rigarukira ku kintu kimwe. Methylene blue ishobora gukangura vuba iyinjira rya glikoze rikorwa na GLUT1 mu turemangingo twa L929, kandi ibyo bigashobora gusubira uko byari bimeze, binyuze mu kwinjira mu karemangingo no mu mikoranire na poroteyine. Ibyo nta cyo bivuga kuri insuline, urwagashya cyangwa isukari yo mu maraso y'inyamaswa nzima. Ku bisobanuro by'iri rangi nk'iritwara electron, reba uko methylene blue ikora nk'itwara electron. Ku mabwiriza yo gusoma ubushakashatsi ku turemangingo, reba uko wasoma ubushakashatsi kuri methylene blue.

Imbeba zirwaye diyabete: imitima yarahindutse, isukari yo mu maraso ntiyahinduka

Ubushakashatsi ku nyamaswa bwimukira ku kindi kintu: umutima w'inyamaswa irwaye diyabete. Ubushakashatsi bwombi ku mbeba bwakoresheje streptozotocin, uburozi bwangiza uturemangingo twa beta dukora insuline, bugatuma habaho imiterere isa na diyabete yo mu bwoko bwa 1. Abasomyi bashaka amakuru kuri methylene blue na diyabete yo mu bwoko bwa 2 bagomba kumenya kuva mu ntangiriro ko ibyo bidahuye. Izi si inyamaswa zirwaye diyabete yo mu bwoko bwa 2.

Mu bushakashatsi bw'igihe kirekire, imbeba z'ingabo zo mu bwoko bwa Lewis zahawe 10 mg kuri kg ku munsi mu mazi yo kunywa mu byumweru 11, hamwe n'ingano nto za insuline zo kubuza umubiri gukendera ariko zidatuma glikoze isubira ku rwego rusanzwe. Muri mitokondiriya z'umutima, irangi ryafashije okisidasiyo ya NADH, ryongera NAD+, kandi ryongera imikorere ya Sirtuin 3 yo gukuraho amatsinda ya acetyl. Isesengura rya poroteyine ryabonye igabanuka ry'ifatana ry'amatsinda ya acetyl ahantu 83 kuri poroteyine 34 za mitokondiriya, ziri mu nzira za okisidasiyo y'ibinure, uruzenguruko rwa aside sitirike n'itwarwa rya electron. Okisidasiyo y'ibinure bifite iminyururu miremire n'imikorere ya hydroxyacyl-CoA dehydrogenase byaragabanutse, bifatwa nk'igabanuka ryo kwishingikiriza birenze kandi bidahinduka ku binure k'umutima urwaye diyabete. Ibipimo by'ingano y'amaraso mu mutima n'umugabane w'amaraso usohorwa n'umutima byateye imbere, kandi igipimo cyerekana kubyimba k'umutima gisubira ku rwego rusanzwe, nubwo umuvuduko w'amaraso n'umuvuduko wo kwikanya byakomeje kuba hasi.

Dore igisubizo cy'ingenzi kurusha ibindi: isukari yo mu maraso ntiyahindutse. Glikoze ipimwa inyamaswa zitariye n'ipimwa zitabanje kwiyiriza byakomeje kuba byinshi; HbA1c yagumye hafi ya 5.6 ku ijana haba mu mbeba zirwaye diyabete zahawe methylene blue no mu zitayihawe, nta ngaruka y'ubuvuzi ifite akamaro mu mibare yagaragaye. Irangi kandi ntiryakosoye inenge yo guhumeka ya complex I na II muri mitokondiriya zari zatandukanyijwe n'uturemangingo. Imikorere y'umutima yateye imbere ku bipimo bimwe, ariko igenzura rya glikoze n'inenge y'ibanze yo guhumeka ntibyateye imbere. Ibisubizo bitandukanye byakomeje gutandukana.

Ubushakashatsi bwa kabiri bwakorewe ku rwego ruto kurushaho: mitokondiriya zatandukanyijwe n'imitima mizima hamwe n'imitima yari imaze amezi abiri irwaye diyabete, zihabwa ingano imwe nto ya 0.1 micromolar mu gihe cyo gupima. Ikoreshwa rya ogisijeni ryiyongereye haba ku bintu bigaburira complex I no ku bigaburira complex II. Ariko irekurwa rya perokiside ya hidurojeni ryatandukanye bitewe n'ibyakoreshejwe nk'isoko y'ingufu: ryiyongereye kuri glutamate hamwe na malate, rigabanuka kuri succinate. Ubushobozi bwo kugumana kalisiyumu ntibwahindutse. Ubu ni ubushakashatsi ku mikorere y'umuti muri mitokondiriya, si igerageza ry'imikorere y'umutima cyangwa rya glikoze. Isomo ritanga ni uko iri rangi ridakumira okisidasiyo mu buryo bumwe mu bihe byose. Kwiyongera cyangwa kugabanuka kw'irekurwa ry'ibintu bitera okisidasiyo biterwa n'icyo mitokondiriya ikoresha mu gukora ingufu. Ku makuru ajyanye n'ibi, reba methylene blue mu bushakashatsi ku mutima n'imiyoboro y'amaraso.

Imbonerahamwe y'icyakoreweho ubushakashatsi n'ibipimo by'ibisubizo: icyageragejwe, icyahindutse n'ikitahindutse

Abantu: amakuru ku isukari yo mu maraso y'abantu ni make cyane

Igerageza rishobora kwiga ibikomere by'abantu barwaye diyabete ritiga igenzura rya glikoze, kandi igikorwa cy'ubuvuzi bw'amenyo gishobora gutangaza HbA1c nk'igipimo cy'inyongera kitagerageza ubuvuzi bwa diyabete.

Igerageza rimwe ryanditswe, NCT05850611, riteganya gutanga methylene blue inyujijwe mu kanwa (70 mg mu mata, ibyumweru bine) ku gisebe cyo ku kirenge cy'umuntu urwaye diyabete, harimo gupima glikoze umuntu atariye, insuline na HbA1c, ariko nta bisubizo rirashyira ahagaragara. Ubushakashatsi buto bw'ibanze bwatangajwe bwahuje umushongi wa plasma ikungahaye ku dusate tw'amaraso hamwe n'ingano nto y'irangi inyujijwe mu kanwa ku gisebe cyo ku kirenge, butangaza ibisubizo ku gikomere no ku rugero rwa ogisijeni, atari ku isukari yo mu maraso. Igerageza ry'ubuvuzi bw'amenyo ryashyize irangi ahantu runaka nk'ikintu cyica mikorobe gikangurwa n'urumuri ku barwayi bafite indwara y'uduce dukikije amenyo na diyabete, ntiryabonye inyungu ifite akamaro mu mibare kuri HbA1c. Irangi rishyizwe mu mufuka wo mu ishinya ritandukanye n'ubuvuzi bw'ihinduramatwara bugera mu mubiri wose; bityo ibyo bisubizo bitagaragaje inyungu na byo nta cyo bivuga ku kurinyuza mu kanwa.

Incamake ivugisha ukuri: nta bimenyetso byatangajwe ku bantu byerekana ko methylene blue ikoreshwa ikagera mu mubiri wose ituma HbA1c, glikoze ipimwa umuntu atariye cyangwa insuline birushaho kugenzurwa neza muri diyabete. Kubura ibimenyetso si gihamya y'uko nta ngaruka ihari, ariko ntibishyigikira iyamamaza rifata iyinjira rya glikoze mu turemangingo cyangwa ibyabonetse mu mitima y'imbeba nk'igihamya cy'igenzura rya glikoze. Ku mbibi z'umutekano zigomba kumenywa mbere y'uko umuntu abigerageza, harimo ibyago bya sindorome ya serotonine igihe ikoreshejwe hamwe n'imiti isanzwe ivura agahinda gakabije, reba umutekano wa methylene blue n'imikoranire yayo n'imiti.

Uko wakoresha ibi bimenyetso utibeshya

Tekereza imashini eshatu. Imashini ya mbere ni irembo rya glikoze mu karemangingo kamwe kororewe muri laboratwari. Imashini ya kabiri ni mitokondiriya yo mu mutima w'imbeba. Imashini ya gatatu ni umuntu urwaye diyabete, ufite urwagashya, umwijima, imikaya, impyiko, imiti n'amafunguro. Byagaragajwe ko iri rangi rigira icyo rihindura ku mashini ya mbere n'iya kabiri. Ntiriragaragazwa ko imashini ya gatatu iryitabira igenzura glikoze neza kurushaho.

Iryo tandukaniro ni ryo rikubiyemo iyi nkuru yose mu gika kimwe. Ikivugwa ku kwita ku barwayi ba diyabete hakoreshejwe methylene blue gishingira ku gukangura poroteyine zitwara glikoze cyangwa ku ifatana ry'amatsinda ya acetyl muri mitokondiriya aho gushingira ku gipimo cy'isukari mu maraso, kiba cyahinduye ingingo. Ibyabonetse kuri Sirtuin 3 na okisidasiyo y'ibinure biracyakwiye gukurikiranwa, ariko igerageza ryo gutegereza ririhariye: igerageza rifite itsinda ryo kugereranya ku bantu barwaye diyabete, ripima HbA1c, glikoze umuntu atariye cyangwa insuline nk'igisubizo cy'ibanze.