Cov ntaub ntawv tshiab hais txog yuav ua li cas Crosstalk ntawm Pancreatic Cells tuaj yeem tsav tsis tshua muaj mob ntshav qab zib

Hauv pancreas, insulin-tsim beta hlwb yog pawg nrog lwm cov tshuaj hormone-tsim endocrine hlwb thiab ncig los ntawm pancreatic exocrine hlwb uas secrete digestive enzymes. Joslin Diabetes Center cov kws tshawb fawb tam sim no tau pom tias yuav ua li cas ib hom kab mob uas tsis tshua muaj tshwm sim hu ua mature pib mob ntshav qab zib mellitus (MODY) yog tsav los ntawm kev hloov pauv digestive enzymes tsim nyob rau hauv pancreatic exocrine hlwb uas tau coj los ntawm cov neeg nyob sib ze insulin-secreting beta hlwb.

Qhov kev tshawb pom no tuaj yeem pab nkag siab txog lwm yam kab mob ntawm cov txiav, suav nrog hom 1 lossis hom 2 mob ntshav qab zib, uas txawv txav ntawm cov kab mob sib kis ntawm ob pawg ntawm cov hlwb no tuaj yeem ua lub luag haujlwm tsis zoo, hais tias Joslin tus kws tshawb fawb laus Rohit N. Kulkarni, MD, PhD, Co-Section Tus Thawj Coj ntawm Joslin's Islet thiab Regenerative Biology Seem thiab tus xibfwb ntawm cov tshuaj hauv Harvard Medical School.

Feem ntau cov qauv ntawm MODY yog tshwm sim los ntawm ib qho kev hloov pauv hauv cov noob qhia cov proteins hauv beta hlwb. Tab sis nyob rau hauv ib daim ntawv ntawm MODY hu ua MODY8, ib tug mutated noob nyob rau hauv lub exocrine hlwb nyob ze paub tias yuav ncaws tawm qhov kev puas tsuaj no, hais tias Kulkarni, coj tus sau ntawm ib tug xwm txheej Metabolism ntawv nthuav qhia txoj hauj lwm. Cov kws tshawb fawb hauv nws lub chaw kuaj pom tau pom tias hauv MODY8, digestive enzymes tsim los ntawm cov noob hloov pauv hauv cov beta hlwb thiab ua rau lawv txoj kev noj qab haus huv thiab kev tso tawm cov tshuaj insulin.

Sevim Kahraman, PhD, tus kws tshawb fawb tom qab kws kho mob hauv Kulkarni lab thiab tus thawj coj ntawm daim ntawv hais tias "Thaum cov kab mob endocrine thiab exocrine pancreas tsim ob qhov sib txawv nrog kev ua haujlwm tsis sib xws, lawv txoj kev sib raug zoo ntawm lub cev ua rau lawv txoj hmoo," "Cov kab mob pathological tsim hauv ib feem cuam tshuam rau lwm qhov."

Anders Molven, PhD, tus kws sau ntawv txhawb nqa thiab xibfwb ntawm University of Bergen hauv Norway hais tias "Txawm hais tias MODY8 yog ib yam kab mob tsawg heev, nws tuaj yeem pom cov txheej txheem dav dav hauv kev txhim kho ntshav qab zib," "Peb qhov kev tshawb pom pom tau tias yuav ua li cas cov txheej txheem kab mob uas pib hauv exocrine pancreas nws thiaj li cuam tshuam rau cov insulin-tsim beta-cells. Peb xav tias qhov tsis zoo ntawm exocrine-endocrine crosstalk tuaj yeem cuam tshuam tshwj xeeb rau kev nkag siab qee qhov mob ntshav qab zib hom 1. "

Kulkarni piav qhia tias qhov hloov pauv CEL (carboxyl ester lipase) gene hauv MODY8 kuj yog suav tias yog cov noob caj ces rau hom ntshav qab zib hom 1. Qhov ntawd ua rau muaj lus nug seb puas muaj qee kis mob ntshav qab zib hom 1 tseem muaj cov protein sib xyaw ua ke hauv beta hlwb, nws hais.

Txoj kev tshawb no pib los ntawm kev hloov kho tib neeg exocrine (acinar) cell kab los qhia txog cov mutant CEL protein. Thaum beta hlwb tau da dej hauv kev daws teeb meem los ntawm kev hloov pauv lossis ib txwm exocrine hlwb, beta hlwb tau coj mus rau ob qho tib si hloov pauv thiab ib txwm muaj proteins, nqa cov protein ntau dua. Cov proteins ib txwm raug degraded los ntawm cov txheej txheem tsis tu ncua hauv cov beta hlwb thiab ploj mus dhau ob peb teev, tab sis cov proteins mutant tsis tau, hloov ua cov protein sib xyaw.

Yog li cas cov aggregates no cuam tshuam rau kev ua haujlwm thiab kev noj qab haus huv ntawm beta hlwb li cas? Hauv kev sim ntau, Kahraman thiab nws cov npoj yaig tau ua pov thawj tias cov hlwb tsis tso cov tshuaj insulin raws li qhov xav tau, proliferated qeeb dua thiab muaj peev xwm ua rau tuag taus.

Nws tau lees paub cov kev tshawb pom no los ntawm cov kab ntawm tes nrog kev sim hauv cov hlwb los ntawm tib neeg pub dawb. Tom qab ntawd, nws tau hloov pauv tib neeg exocrine hlwb (dua qhia txog kev hloov pauv lossis ib txwm digestive enzyme) nrog rau tib neeg beta hlwb rau hauv tus qauv nas tsim los txais tib neeg lub hlwb. Kulkarni tau hais tias "Txawm tias nyob rau hauv qhov xwm txheej ntawd, nws tuaj yeem pom tau tias cov protein hloov pauv tau rov ua dua los ntawm beta cell piv rau cov protein ib txwm, thiab nws tsim cov aggregates insoluble," Kulkarni tau hais.

Tsis tas li ntawd, tshuaj xyuas pancreases los ntawm cov neeg uas muaj MODY8 uas tau tuag los ntawm lwm cov laj thawj, cov kws tshawb nrhiav pom tias cov beta hlwb muaj cov protein hloov pauv. "Hauv cov neeg pub noj qab haus huv, peb tsis pom txawm tias cov protein ib txwm nyob hauv beta cell," nws hais.

Helge Raeder, MD, tus kws sau ntawv thiab xibfwb ntawm University of Bergen tau hais tias "Zaj MODY8 zaj dab neeg no tau pib nrog kev soj ntsuam soj ntsuam ntawm cov neeg mob ntshav qab zib kuj muaj teeb meem digestive, uas coj mus rau kev tshawb nrhiav cov noob caj noob ces," said Helge Raeder, MD, tus kws sau ntawv thiab xibfwb ntawm University of Bergen. "Nyob rau hauv txoj kev tshawb no tam sim no, peb kaw lub voj voog los ntawm kev sib txuas cov kev tshawb fawb soj ntsuam no. Raws li peb qhov kev cia siab, lub plab zom mov uas ib txwm ua rau lub plab tau hloov pauv mus rau hauv cov islet pancreatic hauv lub xeev muaj mob, thaum kawg cuam tshuam rau kev tso tawm insulin. "

Niaj hnub no, cov neeg mob MODY8 tau kho nrog tshuaj insulin lossis tshuaj ntshav qab zib qhov ncauj. Kulkarni thiab nws cov npoj yaig yuav nrhiav txoj hauv kev los tsim kho kom haum thiab kho tus kheej. "Piv txwv li, peb puas tuaj yeem yaj cov protein sib sau ua ke, lossis txwv lawv cov kev sib sau ua ke hauv beta cell?" nws hais. "Peb tuaj yeem coj cov lus qhia los ntawm qhov tau kawm hauv lwm yam kab mob xws li Alzheimer's disease thiab Parkinson's disease uas muaj cov txheej txheem sib sau ua ke zoo sib xws hauv cov hlwb."

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