42-OR: Hub Cells Orchestrate 3-Dimensional Pancreatic Beta-Cell Ca2+ Dynamics In Vivo

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 42-OR
Author(s):  
VICTORIA SALEM ◽  
LUIS F. DELGADILLO SILVA ◽  
KINGA SUBA ◽  
ALDARA MARTIN ALONSO ◽  
WHEI-CHANG KIM ◽  
...  
1994 ◽  
Vol 94 (4) ◽  
pp. 1456-1462 ◽  
Author(s):  
J M N'Guyen ◽  
C Magnan ◽  
M C Laury ◽  
C Thibault ◽  
J Leveteau ◽  
...  

2018 ◽  
Author(s):  
Victoria Salem ◽  
Kinga Suba ◽  
Aldara Martin-Alonso ◽  
Delgadillo Silva Luis Fernando ◽  
Nadeem Akhtar ◽  
...  

Diabetologia ◽  
1993 ◽  
Vol 36 (7) ◽  
pp. 589-595 ◽  
Author(s):  
C. Thibault ◽  
C. Guettet ◽  
M. C. Laury ◽  
J. M. N'Guyen ◽  
M. A. Tormo ◽  
...  

2019 ◽  
Vol 241 (1) ◽  
pp. 45-57 ◽  
Author(s):  
A Edlund ◽  
M Barghouth ◽  
M Hühn ◽  
M Abels ◽  
J S E Esguerra ◽  
...  

Cystic fibrosis-related diabetes (CFRD) is a common complication for patients with cystic fibrosis (CF), a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). The cause of CFRD is unclear, but a commonly observed reduction in first-phase insulin secretion suggests defects at the beta cell level. Here we aimed to examine alpha and beta cell function in the Cftr tm1 EUR/F508del mouse model (C57BL/6J), which carries the most common human mutation in CFTR, the F508del mutation. CFTR expression, beta cell mass, insulin granule distribution, hormone secretion and single cell capacitance changes were evaluated using islets (or beta cells) from F508del mice and age-matched wild type (WT) mice aged 7–10 weeks. Granular pH was measured with DND-189 fluorescence. Serum glucose, insulin and glucagon levels were measured in vivo, and glucose tolerance was assessed using IPGTT. We show increased secretion of proinsulin and concomitant reduced secretion of C-peptide in islets from F508del mice compared to WT mice. Exocytosis and number of docked granules was reduced. We confirmed reduced granular pH by CFTR stimulation. We detected decreased pancreatic beta cell area, but unchanged beta cell number. Moreover, the F508del mutation caused failure to suppress glucagon secretion leading to hyperglucagonemia. In conclusion, F508del mice have beta cell defects resulting in (1) reduced number of docked insulin granules and reduced exocytosis and (2) potential defective proinsulin cleavage and secretion of immature insulin. These observations provide insight into the functional role of CFTR in pancreatic islets and contribute to increased understanding of the pathogenesis of CFRD.


2020 ◽  
Vol 103 ◽  
pp. 3-13 ◽  
Author(s):  
Claire Wen Ying Neo ◽  
Larissa Miasiro Ciaramicoli ◽  
Andreas Alvin Purnomo Soetedjo ◽  
Adrian Kee Keong Teo ◽  
Nam-Young Kang

2010 ◽  
Vol 16 (14) ◽  
pp. 1609-1618 ◽  
Author(s):  
Thomas Bouckenooghe ◽  
Daisy Flamez ◽  
Fernanda Ortis ◽  
Serge Goldman ◽  
Decio L. Eizirik

Sign in / Sign up

Export Citation Format

Share Document