Mupancreas, masero ebeta anogadzira insulin anosanganiswa nemamwe masero eendocrine anogadzira mahormone uye akakomberedzwa nepancreatic exocrine masero anoburitsa ma enzymes ekugaya. Vatsvagiri veJoslin Diabetes Center parizvino vakaratidza nzira imwe yechirwere chisingawanzogarwa nhaka chinozivikanwa sechirwere cheshuga chevadiki (MODY) chinofambiswa nema enzymes ekudya anogadzirwa mupancreatic exocrine masero anozotorwa nevavakidzani ve insulin-secreting beta masero.
Kuwana uku kunogona kubatsira mukunzwisisa zvimwe zvirwere zvepancreas, kusanganisira rudzi rwekutanga kana 1 chirwere cheshuga, umo zvisingawanzoitiki ma molecular crosstalk pakati pemapoka maviri aya emasero zvinogona kuita zvinokuvadza, akadaro Joslin muongorori mukuru Rohit N. Kulkarni, MD, PhD. Co-Chikamu Musoro weJoslin's Islet uye Regenerative Biology Chikamu uye Purofesa weMishonga paHarvard Medical School.
Mazhinji mavhezheni eMODY anokonzerwa nekuchinja kumwe chete mumajeni anoratidza mapuroteni mumaseru ebeta. Asi mune imwe fomu yeMODY inonzi MODY8, geni rakashandurwa mumasero exocrine riri pedyo rinozivikanwa kutanga maitiro ekukuvadza aya, akadaro Kulkarni, munyori anoenderana neNature Metabolism bepa achipa basa. Masayendisiti murabhoritari yake akawana kuti muMODY8, ma enzymes ekugaya anogadzirwa neiyi mutated gene aggregate mumaseru ebeta uye kukanganisa hutano hwavo uye insulin-kuburitsa basa.
"Nepo endocrine uye exocrine pancreas ichiumba zvikamu zviviri zvakasiyana zvine mabasa akasiyana, hukama hwavo hwepedyo hwechimiro hunoumba mafambiro avo," akadaro Sevim Kahraman, PhD, muongorori wepashure muKulkarni lab uye munyori anotungamira webepa. "Mamiriro ehutano ari kukura mune chimwe chikamu anokanganisa chimwe."
"Kunyangwe MODY8 chiri chirwere chisingawanzoitiki, chinogona kujekesa nzira dzese dzinobatanidzwa mukukura kwechirwere cheshuga," akadaro Anders Molven, PhD, munyori anobatsira uye Purofesa paYunivhesiti yeBergen kuNorway. "Zvatinowana zvinoratidza kuti chirongwa chechirwere chinotanga mune exocrine pancreas chinozopedzisira chakanganisa mabeta-seli anoburitsa insulin. Isu tinofunga kuti zvakashata zvakadaro exocrine-endocrine crosstalk inogona kunyanya kukosha pakunzwisisa zvimwe zviitiko zvechirwere cheshuga chekutanga.
Kulkarni akatsanangura kuti iyo yakashandurwa CEL (carboxyl ester lipase) gene muMODY8 zvakare inoonekwa senjodzi yerudzi rwekutanga chirwere cheshuga. Izvi zvinomutsa mubvunzo wekuti dzimwe nyaya dzechirwere cheshuga cherudzi rwekutanga dzinoratidzawo mapuroteni aya akasanganiswa mumasero e beta, akadaro.
Chidzidzo ichi chakatanga nekugadzirisa mutsara wesero remunhu exocrine (acinar) kuratidza mutant CEL protein. Pakagezwa masero e beta mumhinduro kubva kune akachinja kana akajairwa exocrine maseru, masero ebeta akatora ese akachinja uye akajairwa mapuroteni, achiunza huwandu hwepamusoro hwemapuroteni akachinja. Iwo mapuroteni akajairwa akashatiswa nemaitiro akajairwa mumaseru ebeta uye akanyangarika kwemaawa akati wandei, asi mapuroteni anochinja haana, panzvimbo pacho achigadzira mapuroteni akaunganidzwa.
Saka aya akaunganidzwa akakanganisa sei basa uye hutano hwemaseru ebeta? Mukutevedzana kwekuyedza, Kahraman nevamwe vake vakaratidza kuti maseru haana kuburitsa insulin paidiwa, akawedzera zvishoma nezvishoma uye aive panjodzi yerufu.
Akasimbisa zvakawanikwa izvi kubva kumasero mitsara nekuyedza mumaseru kubva kune vanhu vanopa. Zvadaro, akadyara exocrine masero emunhu (zvakare achiratidza angave akachinja kana akajairwa digestive enzyme) pamwe nemasero ebeta evanhu kuita modhi yembeva yakagadzirirwa kugamuchira maseru emunhu. "Kunyangwe mumamiriro ezvinhu aya, anogona kuratidza kuti puroteni yakashandurwa inotorwa zvakare nebeta cell kana ichienzaniswa neprotein yakajairwa, uye inoumba aggregates asinganyungudika," akadaro Kulkarni.
Pamusoro pezvo, vachiongorora pancreas kubva kuvanhu vane MODY8 vakafa kubva kune zvimwe zvikonzero, vaongorori vakaona kuti masero ebeta aive neprotein yakashandurwa. "Muvanopa vane hutano, hatina kuwana chero puroteni yakajairwa mubeta cell," akadaro.
"Nyaya iyi yeMODY8 yakatanga nekuonekwa kwekiriniki kwevarwere vane chirwere cheshuga vane matambudziko ekugaya, izvo zvakakonzera kuwanikwa kweiyo genetic denominator," akadaro Helge Raeder, MD, munyori-munyori uye Purofesa paYunivhesiti yeBergen. “Muchidzidzo chazvino, tinovhara denderedzwa nekubatanidza zvine hungwaru zvakawanikwa zvekiriniki izvi. Kusiyana nezvataitarisira, enzyme yekugaya yaiwanzo kugadzirirwa ura yakatsauswa kuti ipinde mupancreatic islet mune chirwere, pakupedzisira ichikanganisa kugadzirwa kwe insulin.
Nhasi, vanhu vane MODY8 vanorapwa ne insulin kana mishonga yechirwere cheshuga yemuromo. Kulkarni nevamwe vake vanozotsvaga nzira dzekugadzira dzakarongedzerwa uye dzemunhu kurapwa. "Semuenzaniso, tinogona here kunyungudutsa aya maprotein aggregates, kana kudzikamisa kuunganidzwa kwawo mubeta cell?" akati. "Tinogona kutora mazano kubva kune zvakadzidzwa mune zvimwe zvirwere zvakaita seAlzheimer's disease uye Parkinson's disease ine maitiro akafanana ekuunganidza mumaseru."
ZVOKUBVA MUNYAYA INO:
- When beta cells were bathed in solution from either mutated or normal exocrine cells, the beta cells took up both the mutated and normal proteins, bringing in higher numbers of the mutated proteins.
- But in one form of MODY called MODY8, a mutated gene in nearby exocrine cells is known to kick off this damaging process, said Kulkarni, corresponding author on a Nature Metabolism paper presenting the work.
- “Even in that scenario, she could show that the mutated protein is again taken up more by the beta cell in comparison to the normal protein, and it forms insoluble aggregates,”.
