Imperial College London
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Dr Alejandra Tomas

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3364a.tomas-catala Website CV

 
 
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Location

 

329ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Georgiadou:2022:10.2337/db21-0800,
author = {Georgiadou, E and Muralidharan, C and Martinez, M and Chabosseau, P and Akalestou, E and Tomas, A and Yong, Su Wern F and Stylianides, T and Wretlind, A and Legido-Quigley, C and Jones, B and Lopez, Noriega L and Xu, Y and Gu, G and Alsabeeh, N and Cruciani-Guglielmacci, C and Magnan, C and Ibberson, M and Leclerc, I and Ali, Y and Soleimanpour, SA and Linnemann, AK and Rodriguez, TA and Rutter, GA},
doi = {10.2337/db21-0800},
journal = {Diabetes},
pages = {1472--1489},
title = {Mitofusins Mfn1 and Mfn2 are required to preserve glucose- but not incretin-stimulated beta cell connectivity and insulin secretion},
url = {http://dx.doi.org/10.2337/db21-0800},
volume = {71},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Mitochondrial glucose metabolism is essential for stimulated insulin release from pancreatic beta cells. Whether mitofusin gene expression, and hence mitochondrial network integrity, is important for glucose or incretin signalling has not previously been explored. Here, we generated mice with beta cell-selective, adult-restricted deletion of the mitofusin genes Mfn1 and Mfn2 (βMfn1/2 dKO). βMfn1/2 dKO mice displayed elevated fed and fasted glycaemia and a >five-fold decrease in plasma insulin. Mitochondrial length, glucose-induced polarisation, ATP synthesis, cytosolic and mitochondrial Ca2+ increases were all reduced in dKO islets. In contrast, oral glucose tolerance was more modestly affected in βMfn1/2 dKO mice and GLP-1 or GIP receptor agonists largely corrected defective GSIS through enhanced EPAC-dependent signalling. Correspondingly, cAMP increases in the cytosol, as measured with an Epac-camps based sensor, were exaggerated in dKO mice. Mitochondrial fusion and fission cycles are thus essential in the beta cell to maintain normal glucose, but not incretin, sensing. These findings broaden our understanding of the roles of mitofusins in beta cells, the potential contributions of altered mitochondrial dynamics to diabetes development and the impact of incretins on this process.
AU  - Georgiadou,E
AU  - Muralidharan,C
AU  - Martinez,M
AU  - Chabosseau,P
AU  - Akalestou,E
AU  - Tomas,A
AU  - Yong,Su Wern F
AU  - Stylianides,T
AU  - Wretlind,A
AU  - Legido-Quigley,C
AU  - Jones,B
AU  - Lopez,Noriega L
AU  - Xu,Y
AU  - Gu,G
AU  - Alsabeeh,N
AU  - Cruciani-Guglielmacci,C
AU  - Magnan,C
AU  - Ibberson,M
AU  - Leclerc,I
AU  - Ali,Y
AU  - Soleimanpour,SA
AU  - Linnemann,AK
AU  - Rodriguez,TA
AU  - Rutter,GA
DO  - 10.2337/db21-0800
EP  - 1489
PY  - 2022///
SN  - 0012-1797
SP  - 1472
TI  - Mitofusins Mfn1 and Mfn2 are required to preserve glucose- but not incretin-stimulated beta cell connectivity and insulin secretion
T2  - Diabetes
UR  - http://dx.doi.org/10.2337/db21-0800
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35472764
UR  - https://diabetesjournals.org/diabetes/article/71/7/1472/145040/Mitofusins-Mfn1-and-Mfn2-Are-Required-to-Preserve
UR  - http://hdl.handle.net/10044/1/96865
VL  - 71
ER  -
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