A cikin pancreas, ƙwayoyin beta masu samar da insulin sun taru tare da wasu ƙwayoyin endocrin masu samar da hormone kuma suna kewaye da ƙwayoyin exocrine na pancreatic waɗanda ke ɓoye enzymes masu narkewa. Masu bincike na Cibiyar Ciwon sukari ta Joslin yanzu sun nuna yadda nau'i ɗaya na cututtukan gada da ba kasafai ake samun su ba da aka sani da balagagge farkon ciwon sukari na matasa (MODY) ke motsa su ta rikitattun enzymes na narkewa da aka samar a cikin sel exocrine na pancreatic waɗanda ke ɗauke da ƙwayoyin beta masu ɓoye insulin.

Wannan binciken na iya taimakawa wajen fahimtar wasu cututtuka na pancreas, ciki har da nau'in 1 ko nau'in ciwon sukari na 2, wanda rashin daidaituwa na kwayoyin halitta tsakanin wadannan rukunoni biyu na kwayoyin halitta na iya taka rawa mai lalacewa, in ji babban jami'in Joslin Rohit N. Kulkarni, MD, PhD. Shugaban Sashen Co-Section na Joslin's Islet da Regenerative Biology Sashin kuma Farfesa na Magunguna a Makarantar Kiwon Lafiya ta Harvard.

Yawancin nau'ikan MODY suna faruwa ta hanyar maye gurbi guda ɗaya a cikin kwayoyin halittar da ke bayyana sunadaran a cikin ƙwayoyin beta. Amma a cikin wani nau'i na MODY da ake kira MODY8, rikitaccen kwayar halitta a cikin sel exocrine kusa an san shi zai fara wannan mummunan tsari, in ji Kulkarni, mawallafin mawallafi a kan takardar Halittar Halittu da ke gabatar da aikin. Masana kimiyya a cikin dakin gwaje-gwajensa sun gano cewa a cikin MODY8, enzymes na narkewar abinci da wannan gurɓataccen ƙwayar cuta ya haifar a cikin ƙwayoyin beta kuma suna lalata lafiyarsu da aikin sakin insulin.

"Yayin da endocrin pancreatic da exocrine pancreatic ke samar da sassa biyu daban-daban tare da ayyuka daban-daban, dangantakar da ke kusa da su tana tsara makomar su," in ji Sevim Kahraman, PhD, mai bincike na postdoctoral a cikin Kulkarni lab kuma marubucin marubucin takarda. "Yanayin pathological da ke tasowa a bangare ɗaya yana lalata ɗayan."

"Ko da yake MODY8 cuta ce da ba kasafai ba, yana iya ba da haske kan hanyoyin gama gari da ke tattare da haɓakar ciwon sukari," in ji Anders Molven, PhD, marubuci mai ba da gudummawa kuma Farfesa a Jami'ar Bergen a Norway. "Bincikenmu ya nuna yadda tsarin cututtuka da ke farawa a cikin exocrine pancreas zai iya shafar kwayoyin beta masu samar da insulin. Muna tsammanin irin wannan mummunan exocrine-endocrine crosstalk na iya zama dacewa musamman don fahimtar wasu lokuta na nau'in ciwon sukari na 1. "

Kulkarni ya bayyana cewa kwayar halittar CEL (carboxyl ester lipase) da aka canza a cikin MODY8 ita ma ana daukarta a matsayin kwayar hadarin kamuwa da ciwon sukari na 1. Wannan ya haifar da tambayar ko wasu lokuta na nau'in ciwon sukari na 1 suma sun ƙunshi waɗannan tarin sunadarai na mutant a cikin ƙwayoyin beta, in ji shi.

An fara binciken ne ta hanyar gyara layin tantanin halitta exocrine (acinar) don bayyana mutant CEL protein. Lokacin da aka yi wa ƙwayoyin beta wanka da bayani daga ko dai gyaɗa ko sel exocrine na yau da kullun, sel beta sun ɗauki duka rikitattun sunadaran da na yau da kullun, suna kawo adadi mafi girma na sunadarai masu maye. Sunadaran sunadaran sun lalace ta hanyar tsari na yau da kullun a cikin ƙwayoyin beta kuma sun ɓace cikin sa'o'i da yawa, amma sunadaran sunadaran ba su yi ba, a maimakon haka suna samar da tarin furotin.

To ta yaya waɗannan tarin suka shafi aiki da lafiyar ƙwayoyin beta? A cikin jerin gwaje-gwajen da aka yi, Kahraman da abokan aikinta sun tabbatar da cewa sel ba sa fitar da insulin kamar yadda ake bukata, suna yaduwa a hankali kuma sun fi saurin mutuwa.

Ta tabbatar da waɗannan binciken daga layin salula tare da gwaje-gwaje a cikin sel daga masu ba da gudummawar ɗan adam. Bayan haka, ta dasa sel exocrine na ɗan adam (sake bayyana ko dai rikiɗar ko na al'ada enzyme) tare da ƙwayoyin beta na ɗan adam a cikin ƙirar linzamin kwamfuta wanda aka ƙera don karɓar ƙwayoyin ɗan adam. "Ko da a cikin wannan yanayin, za ta iya nuna cewa kwayar halittar beta ta sake ɗaukar furotin ɗin da ya rikiɗe idan aka kwatanta da furotin na yau da kullun, kuma yana haifar da tarin abubuwan da ba za a iya narkewa ba," in ji Kulkarni.

Bugu da ƙari, nazarin ƙwayoyin cuta daga mutanen da ke da MODY8 waɗanda suka mutu daga wasu dalilai, masu binciken sun ga cewa ƙwayoyin beta sun ƙunshi furotin da aka canza. "A cikin masu ba da gudummawa lafiya, ba mu sami ko da furotin na yau da kullun a cikin kwayar beta ba," in ji shi.

"Wannan labarin MODY8 ya samo asali ne tare da lura da asibiti na marasa lafiya da ciwon sukari kuma suna da matsalolin narkewa, wanda ya haifar da gano nau'in kwayoyin halitta," in ji Helge Raeder, MD, marubucin marubuci kuma Farfesa a Jami'ar Bergen. "A cikin binciken na yanzu, muna rufe da'irar ta hanyar haɗa waɗannan binciken na asibiti. Sabanin abin da muke tsammani, wani enzyme mai narkewa wanda aka tsara don hanji a maimakon haka an yaudare shi don shiga tsibirin pancreatic a cikin yanayin rashin lafiya, wanda a ƙarshe ya lalata ƙwayar insulin.

A yau, ana yi wa mutanen da ke da MODY8 magani da insulin ko magungunan ciwon sukari na baki. Kulkarni da abokan aikinsa za su nemo hanyoyin da za su ƙirƙira ingantattun hanyoyin warkewa na musamman. "Alal misali, shin zamu iya narkar da waɗannan tarin furotin, ko iyakance haɗin su a cikin tantanin halitta beta?" Yace. "Za mu iya yin la'akari daga abin da aka koya a wasu cututtuka kamar cutar Alzheimer da cutar Parkinson da ke da irin wannan tsarin tarawa a cikin sel."

ABUBUWAN DA ZA KU GUDU DAGA WANNAN LABARI:

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,”.