Ulwazi olutsha malunga nokuba i-Crosstalk phakathi kweeSeli zePancreatic inokuQhuba njani uhlobo olunqabileyo lwesifo seswekile

Ibhalwe ngu umhleli

Ii-enzymes zokwetyisa eziguquguqukayo ziyadibana kwiiseli ze-beta ezivelisa i-insulin, nto leyo ebangela imeko efunyenwe njengelifa enokuthi ikhanyisele ezinye izifo ze-pancreas.

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Kwi-pancreas, iiseli ze-beta ezivelisa i-insulin zidityaniswe nezinye iiseli ze-endocrine ezivelisa ihomoni kwaye zijikelezwe ziiseli ze-pancreatic exocrine ezikhupha ii-enzymes zokugaya ukutya. Abaphandi beJoslin Diabetes Centre ngoku baye babonisa indlela olunye uhlobo lwesifo esinqabileyo esizuzwe njengesifo seswekile esivuthiweyo solutsha (MODY) siqhutywa zii-enzymes zokugaya ukutya ezenziwe kwiiseli ze-pancreatic exocrine ezithi ke zithathwe ziiseli ze-beta ezingabamelwane.

Oku kufunyaniswa kunokunceda ekuqondeni ezinye izifo ze-pancreas, kubandakanywa uhlobo lwe-1 okanye uhlobo lwe-2 yeswekile, apho i-molecular crosstalk engaqhelekanga phakathi kwala maqela amabini eeseli inokudlala indima eyonakalisayo, utshilo umphandi ophezulu waseJoslin uRohit N. Kulkarni, MD, PhD, INtloko yeCandelo le-Co-Section ye-Joslin's Islet kunye neCandelo leBhayoloji yokuhlaziya kunye noNjingalwazi wezoNyango kwiSikolo sezoNyango saseHarvard.

Uninzi lweenguqulelo zeMODY zibangelwa kukuguqulwa kofuzo olunye olubonisa iiproteni kwiiseli ze-beta. Kodwa kuhlobo olunye lwe-MODY ebizwa ngokuba yi-MODY8, ijini eguqulweyo kwiiseli ze-exocrine ezikufutshane yaziwa ngokuqalisa le nkqubo yokonakalisa, utshilo u-Kulkarni, umbhali ohambelanayo kwiphepha le-Nature Metabolism ebonisa umsebenzi. Izazinzulu kwilebhu yakhe zafumanisa ukuba kwi-MODY8, ii-enzymes zokwetyisa eziveliswa yile mfuza iguqukileyo edityanisiweyo kwiiseli ze-beta kwaye zonakalise impilo yazo kunye nomsebenzi wokukhupha i-insulin.

"Ngelixa i-endocrine kunye ne-exocrine pancreas zenza iindawo ezimbini ezihlukeneyo ezinemisebenzi eyahlukileyo, ubudlelwane babo obusondeleyo be-anatomical bubumba ikamva labo," utshilo uSevim Kahraman, PhD, umphandi we-postdoctoral kwilebhu yaseKulkarni kunye nombhali okhokelayo wephepha. "Imeko ye-pathological ekhula kwindawo enye iyonakalisa enye."

"Nangona i-MODY8 isisifo esinqabileyo kakhulu, inokukhanyisa kwiindlela eziqhelekileyo ezibandakanyekayo ekuphuhliseni isifo seswekile," kusho uAnders Molven, PhD, umbhali onegalelo kunye noNjingalwazi kwiYunivesithi yaseBergen eNorway. “Iziphumo zethu zibonisa ukuba inkqubo yesifo eqala kwi-exocrine pancreas ekugqibeleni inokuchaphazela njani iiseli ze-beta ezivelisa i-insulin. Sicinga ukuba i-exocrine-endocrine crosstalk inokuba yinto efanelekileyo ngakumbi ekuqondeni ezinye iimeko zohlobo loku-1 lweswekile. ”

UKulkarni uchaze ukuba i-CEL (carboxyl ester lipase) eguqulweyo yofuzo kwiMODY8 ikwajongwa njengomngcipheko wohlobo loku-1 lweswekile. Oko kuphakamisa umbuzo wokuba ingaba ezinye iimeko zesifo seswekile ezi-1 zikwabonisa ezi proteni zidibeneyo kwiiseli ze-beta, utshilo.

Uphononongo lwaqala ngokuguqula umgca weseli we-exocrine (acinar) ukuze ubonise iprotein ye-CEL eguqukayo. Xa iiseli ze-beta zazihlanjwa kwisisombululo ukusuka kwiiseli eziguquliweyo okanye eziqhelekileyo ze-exocrine, iiseli ze-beta zathatha zombini iiproteni eziguquliweyo neziqhelekileyo, zizisa amanani aphezulu eeproteni ezitshintshiweyo. Iiprotheyini eziqhelekileyo zonakaliswa ziinkqubo eziqhelekileyo kwiiseli ze-beta kwaye zanyamalala kwiiyure ezininzi, kodwa iiprotheyini eziguqukayo azizange zenze, endaweni yoko zenza i-protein aggregates.

Ke ezi zintlanganisela ziwuchaphazele njani umsebenzi kunye nempilo yeeseli ze-beta? Kuthotho lovavanyo, uKahraman kunye noogxa bakhe bangqina ukuba iiseli aziyikhuphi i-insulin kunye nemfuno, zanda kancinci kwaye zisesichengeni sokufa.

Uye waqinisekisa ezi zinto zifunyanisiweyo kwimigca yeeseli ngovavanyo kwiiseli ezivela kubanikeli babantu. Emva koko, wafakela iiseli ze-exocrine zabantu (kwakhona ebonakalisa i-muted okanye i-enzayimi eqhelekileyo yokugaya) kunye neeseli ze-beta zabantu kwimodeli yempuku eyenzelwe ukwamkela iiseli zomntu. "Nakuloo meko, unokubonisa ukuba iprotheni eguqukileyo iphinda ithathwe ngakumbi yiseli ye-beta xa kuthelekiswa neprotheni eqhelekileyo, kwaye yenza i-aggregates enganyibilikiyo," kusho uKulkarni.

Ukongeza, uphononongo lwe-pancreas kubantu abane-MODY8 abasweleke ngenxa yezinye izizathu, abaphandi babona ukuba iiseli ze-beta zineproteni eguqulweyo. “Kubanikeli abasempilweni, asifumananga neprotheyini eqhelekileyo kwiseli ye-beta,” utshilo.

"Eli bali le-MODY8 ekuqaleni laqala ngokuqwalaselwa kweklinikhi yezigulane ezinesifo seswekile nazo zineengxaki zokugaya, ezikhokelela ekufumaneni i-genetic denominator," watsho uHelge Raeder, MD, umbhali-mbhali kunye noNjingalwazi kwiYunivesithi yaseBergen. “Kuphononongo lwangoku, sivala isangqa ngokudibanisa ezi ziphumo zonyango ngoomatshini. Ngokuchaseneyo noko besikulindele, i-enzyme yokwetyisa eqhele ukusetyenziselwa amathumbu endaweni yoko yalahlekiswa ukuba ingene kwi-pancreatic islet kwimeko yokugula, ekugqibeleni ibeka esichengeni ukukhutshwa kwe-insulin.

Namhlanje, abantu abane-MODY8 banyangwa nge-insulin okanye amayeza eswekile yomlomo. U-Kulkarni kunye noogxa bakhe baya kukhangela iindlela zokwenza unyango olulungiselelwe ngakumbi kunye nolwenzelwe wena. "Umzekelo, singayinyibilikisa ezi proteni zidibene, okanye sinciphise ukudityaniswa kwazo kwiseli ye-beta?" uthe. "Singathatha ingcebiso koko kuye kwafundwa kwezinye izifo ezinjenge-Alzheimer's kunye nesifo sika-Parkinson ezinendlela efanayo yokudibanisa kwiiseli."

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Umhleli oyintloko we-eTurboNew nguLinda Hohnholz. Uzinze kwi-eTN HQ e-Honolulu, eHawaii.

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