The mechanisms underlying the effects of exocrine dysfunction on the development of diabetes remain largely unknown. Here, we show that pancreatic depletion of SMAD7 resulted in age-dependent increases in β-cell dysfunction, with accelerated glucose intolerance, followed by overt diabetes. The accelerated β-cell dysfunction and loss of proliferation capacity, two features of β-cell aging, appeared to be non-cell-autonomous, secondary to the adjacent exocrine failure as a bystander effect. Increased FoxO1 acetylation and nuclear retention was followed by progressive FoxO1 loss in β-cells, which marked the onset of diabetes. Moreover, forced FoxO1 expression in β-cells prevented β-cell dysfunction and loss in this model. Thus, we present a model of accelerated β-cell aging, which may be useful for studying the mechanisms underlying β-cell failure in diabetes. Moreover, we provide evidence highlighting a critical role of FoxO1 in maintaining β-cell identity in the context of SMAD7 failure.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ihSWwL
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182, Butyric Acid from Probiotic Staphyloco...
-
Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
-
Medicine by Alexandros G. Sfakianakis,Αλέξανδρος Γ. Σφακιανάκης A Novel Technique for Endoscopic Repair of Large Anterior Skull Base Defect...
-
2016-11-22T07-55-59Z Source: International Journal of Medical Science and Public Health Banothu Srinivas, Madhu Mohan Reddy B. Backgrou...
-
2016-10-15T06-30-01Z Source: The Southeast Asian Journal of Case Report and Review Sangita Deepak Kamath, Neeraj Jain, Saurabh Pathak, Ba...
-
BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with cl...
-
Abstract The development of focused ion beam-scanning electron microscopy (FIB-SEM) techniques has allowed high-resolution 3D imaging of n...
-
Vol.48 No.2 from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1S2Z7n2 via IFTTT
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου