Imperial College London
Alternate

ProfessorGuyRutter

Faculty of Medicine, Department of Medicine

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3340g.rutter Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Solimena:2017:10.1007/s00125-017-4500-3,
author = {Solimena, M and Schulte, AM and Marselli, L and Ehehalt, F and Richter, D and Kleeberg, M and Mziaut, H and Knoch, K-P and Parnis, J and Bugliani, M and Siddiq, A and Jörns, A and Burdet, F and Liechti, R and Suleiman, M and Margerie, D and Syed, F and Distler, M and Grützmann, R and Petretto, E and Moreno-Moral, A and Wegbrod, C and Sönmez, A and Pfriem, K and Friedrich, A and Meinel, J and Wollheim, CB and Baretton, GB and Scharfmann, R and Nogoceke, E and Bonifacio, E and Sturm, D and Meyer-Puttlitz, B and Boggi, U and Saeger, H-D and Filipponi, F and Lesche, M and Meda, P and Dahl, A and Wigger, L and Xenarios, I and Falchi, M and Thorens, B and Weitz, J and Bokvist, K and Lenzen, S and Rutter, GA and Froguel, P and von, Bülow M and Ibberson, M and Marchetti, P},
doi = {10.1007/s00125-017-4500-3},
journal = {Diabetologia},
pages = {641--657},
title = {Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes.},
url = {http://dx.doi.org/10.1007/s00125-017-4500-3},
volume = {61},
year = {2017}
}
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TY  - JOUR
AB  - AIMS/HYPOTHESIS: Pancreatic islet beta cell failure causes type 2 diabetes in humans. To identify transcriptomic changes in type 2 diabetic islets, the Innovative Medicines Initiative for Diabetes: Improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in Diabetes (IMIDIA) consortium ( www.imidia.org ) established a comprehensive, unique multicentre biobank of human islets and pancreas tissues from organ donors and metabolically phenotyped pancreatectomised patients (PPP). METHODS: Affymetrix microarrays were used to assess the islet transcriptome of islets isolated either by enzymatic digestion from 103 organ donors (OD), including 84 non-diabetic and 19 type 2 diabetic individuals, or by laser capture microdissection (LCM) from surgical specimens of 103 PPP, including 32 non-diabetic, 36 with type 2 diabetes, 15 with impaired glucose tolerance (IGT) and 20 with recent-onset diabetes (<1 year), conceivably secondary to the pancreatic disorder leading to surgery (type 3c diabetes). Bioinformatics tools were used to (1) compare the islet transcriptome of type 2 diabetic vs non-diabetic OD and PPP as well as vs IGT and type 3c diabetes within the PPP group; and (2) identify transcription factors driving gene co-expression modules correlated with insulin secretion ex vivo and glucose tolerance in vivo. Selected genes of interest were validated for their expression and function in beta cells. RESULTS: Comparative transcriptomic analysis identified 19 genes differentially expressed (false discovery rate ≤0.05, fold change ≥1.5) in type 2 diabetic vs non-diabetic islets from OD and PPP. Nine out of these 19 dysregulated genes were not previously reported to be dysregulated in type 2 diabetic islets. Signature genes included TMEM37, which inhibited Ca2+-influx and insulin secretion in beta cells, and ARG2 and PPP1R1A, which promoted insulin secretion. Systems biology approaches identified HNF1A, PDX1 and REST as drivers o
AU  - Solimena,M
AU  - Schulte,AM
AU  - Marselli,L
AU  - Ehehalt,F
AU  - Richter,D
AU  - Kleeberg,M
AU  - Mziaut,H
AU  - Knoch,K-P
AU  - Parnis,J
AU  - Bugliani,M
AU  - Siddiq,A
AU  - Jörns,A
AU  - Burdet,F
AU  - Liechti,R
AU  - Suleiman,M
AU  - Margerie,D
AU  - Syed,F
AU  - Distler,M
AU  - Grützmann,R
AU  - Petretto,E
AU  - Moreno-Moral,A
AU  - Wegbrod,C
AU  - Sönmez,A
AU  - Pfriem,K
AU  - Friedrich,A
AU  - Meinel,J
AU  - Wollheim,CB
AU  - Baretton,GB
AU  - Scharfmann,R
AU  - Nogoceke,E
AU  - Bonifacio,E
AU  - Sturm,D
AU  - Meyer-Puttlitz,B
AU  - Boggi,U
AU  - Saeger,H-D
AU  - Filipponi,F
AU  - Lesche,M
AU  - Meda,P
AU  - Dahl,A
AU  - Wigger,L
AU  - Xenarios,I
AU  - Falchi,M
AU  - Thorens,B
AU  - Weitz,J
AU  - Bokvist,K
AU  - Lenzen,S
AU  - Rutter,GA
AU  - Froguel,P
AU  - von,Bülow M
AU  - Ibberson,M
AU  - Marchetti,P
DO  - 10.1007/s00125-017-4500-3
EP  - 657
PY  - 2017///
SN  - 0012-186X
SP  - 641
TI  - Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes.
T2  - Diabetologia
UR  - http://dx.doi.org/10.1007/s00125-017-4500-3
UR  - http://hdl.handle.net/10044/1/54338
VL  - 61
ER  -
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