Ulwazi Olusha Ngokuthi I-Crosstalk Phakathi Kwamangqamuzana E-pancreatic Ingaluqhuba Kanjani Uhlobo Lwesifo Sikashukela Olungavamile

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Ama-enzyme aguquguqukayo okugaya ahlangana kumaseli e-beta akhiqiza i-insulin aseduze, aqale isimo esizuzwe njengefa esingase sikhanyisele ezinye izifo zamanyikwe.

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Kumanyikwe, amaseli e-beta akhiqiza i-insulin ahlanganiswe namanye amaseli e-endocrine akhiqiza amahomoni futhi azungezwe amaseli e-pancreatic exocrine akhiqiza ama-enzyme okugaya. Abacwaningi beJoslin Diabetes Center manje sebekhombisile ukuthi uhlobo olulodwa lwesifo esingajwayelekile esitholwa ngofuzo esaziwa ngokuthi i-mature start diabetes of the young (MODY) luqhutshwa kanjani ama-enzyme okugaya akhiqizwa kumaseli e-pancreatic exocrine abese ethathwa ngamaseli e-beta angomakhelwane akhiqiza i-insulin.

Lokhu kutholakala kungasiza ekuqondeni ezinye izifo ze-pancreas, okuhlanganisa uhlobo 1 noma uhlobo lwe-2 yesifo sikashukela, lapho ukuhlangana okungavamile kwamangqamuzana phakathi kwala maqembu amabili amangqamuzana kungase kudlale indima elimazayo, kusho umphenyi omkhulu kaJoslin uRohit N. Kulkarni, MD, PhD, I-Co-Section Head of Joslin's Islet and Regenerative Biology Section kanye noSolwazi Wezokwelapha e-Harvard Medical School.

Izinguqulo eziningi ze-MODY zidalwe ukuguqulwa okukodwa kofuzo okuveza amaprotheni kumaseli e-beta. Kodwa kolunye uhlobo lwe-MODY olubizwa nge-MODY8, isakhi sofuzo esiguquliwe kumaseli e-exocrine aseduze saziwa ngokuqala le nqubo elimazayo, kusho u-Kulkarni, umbhali ohambisanayo ephepheni le-Nature Metabolism elethula umsebenzi. Ososayensi endaweni yakhe bathole ukuthi ku-MODY8, ama-enzyme okugaya akhiqizwa yile ngxube yofuzo eguquliwe kumaseli e-beta futhi alimaza impilo yawo kanye nomsebenzi wokukhipha i-insulin.

"Ngenkathi i-endocrine kanye ne-exocrine pancreas akha izingxenye ezimbili ezihlukene ezinemisebenzi ehlukene, ubudlelwano bawo obuseduze be-anatomical balolonga isiphetho sazo," kusho uSevim Kahraman, PhD, umcwaningi we-postdoctoral elebhu yaseKulkarni nombhali oholayo wephepha. "Isimo se-pathological esenzeka engxenyeni eyodwa silimaza enye."

“Nakuba i-MODY8 iyisifo esiyivelakancane, ingase isikhanyisele ngezindlela ezivamile ezihilelekile ekuthuthukisweni kwesifo sikashukela,” kusho u-Anders Molven, PhD, umbhali onikelayo noProfessor eNyuvesi yaseBergen eNorway. “Okutholakele kwethu kukhombisa ukuthi inqubo yesifo eqala kumanyikwe exocrine ekugcineni ingawathinta kanjani amaseli e-beta akhiqiza i-insulin. Sicabanga ukuthi i-exocrine-endocrine crosstalk engeyinhle kangako ingabaluleka kakhulu ekuqondeni ezinye izimo zesifo sikashukela sohlobo loku-1. ”

UKulkarni uchaze ukuthi ufuzo oluguquliwe lwe-CEL (carboxyl ester lipase) ku-MODY8 nalo luthathwa njengofuzo oluyingozi kuhlobo loku-1 lwesifo sikashukela. Lokho kuphakamisa umbuzo wokuthi ngabe ezinye izimo zesifo sikashukela sohlobo loku-1 nazo ziyawafaka yini lawa maprotheni ahlanganisiwe aguquguqukayo kumaseli e-beta, esho.

Ucwaningo lwaqala ngokushintsha umugqa weseli womuntu we-exocrine (acinar) ukuze uveze iphrotheni ye-CEL eguquguqukayo. Lapho amaseli e-beta egezwa ngesisombululo kusuka kumaseli e-exocrine aguquliwe noma avamile, amaseli e-beta athatha kokubili amaprotheni aguquliwe navamile, aletha amanani aphezulu amaprotheni aguquliwe. Amaprotheni avamile wonakaliswa izinqubo ezivamile kumaseli e-beta futhi anyamalala emahoreni ambalwa, kodwa amaprotheni aguqukayo awazange, esikhundleni salokho akhe ama-protein aggregate.

Ngakho-ke lezi zibalo ziwuthinte kanjani umsebenzi nempilo yamaseli e-beta? Ochungechungeni lwezivivinyo, u-Kahraman nozakwabo bafakazele ukuthi amaseli awayikhiphi i-insulin uma idingeka, anda kancane kakhulu futhi aba sengozini yokufa.

Uqinisekise lokhu okutholwe kumaseli ngokuhlolwa kwamaseli avela kubanikeli abangabantu. Okulandelayo, watshala amaseli e-exocrine womuntu (ephinde eveza i-enzyme eguquliwe noma evamile yokugaya) kanye namaseli e-beta omuntu enze imodeli yegundane eklanyelwe ukwamukela amaseli omuntu. "Ngisho nakuleso simo, angakhombisa ukuthi iphrotheni eguquliwe iphinde ithathwe kakhulu yiseli ye-beta uma iqhathaniswa nephrotheni evamile, futhi yakha ama-aggregate angancibiliki," kusho u-Kulkarni.

Ukwengeza, lapho behlola amanyikwe avela kubantu abane-MODY8 abashona ngenxa yezinye izimbangela, abaphenyi babona ukuthi amaseli e-beta aqukethe amaprotheni aguquliwe. “Kubanikeli abanempilo enhle, asizange sithole ngisho nephrotheni evamile kuseli ye-beta,” esho.

"Le ndaba ye-MODY8 ekuqaleni iqale ngokubhekwa emtholampilo kweziguli ezinesifo sikashukela nazo ezinezinkinga zokugaya ukudla, okuholele ekutholakaleni kofuzo olujwayelekile," kusho u-Helge Raeder, MD, umbhali kanye noProfessor eNyuvesi yaseBergen. “Ocwaningweni lwamanje, sivala umbuthano ngokuxhumanisa lezi zinto ezitholwe emitholampilo ngokwemishini. Ngokuphambene nalokho ebesikulindele, i-enzyme yokugaya ukudla evame ukusetshenziselwa amathumbu esikhundleni sayo yadukiswa ukuthi ingene esiqhingini se-pancreatic esisesimweni sokugula, ekugcineni ibeke engcupheni ukukhiqizwa kwe-insulin.

Namuhla, abantu abane-MODY8 belashwa nge-insulin noma imishanguzo yesifo sikashukela somlomo. U-Kulkarni nozakwabo bazobheka izindlela zokuklama izindlela zokwelapha ezifanelana kakhulu neziqondene nawe. "Isibonelo, singahlakaza lezi zibalo zamaprotheni, noma sinciphise ukuhlangana kwazo kuseli ye-beta?" uthe. "Singathatha izinkomba kulokho okufundiwe kwezinye izifo ezinjenge-Alzheimer's kanye nesifo sika-Parkinson ezinomshini ofanayo wokuhlanganisa emangqamuzaneni."

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