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Aichler, M. ; Borgmann, D.M. ; Krumsiek, J. ; Buck, A. ; MacDonald, P.E.* ; Fox, J.E.M.* ; Lyon, J.* ; Light, P.E.* ; Keipert, S. ; Jastroch, M. ; Feuchtinger, A. ; Müller, N.S. ; Sun, N. ; Palmer, A.* ; Alexandrov, T.* ; Hrabě de Angelis, M. ; Neschen, S. ; Tschöp, M.H. ; Walch, A.K.

N-acyl taurines and acylcarnitines cause an imbalance in insulin synthesis and secretion provoking β cell dysfunction in type 2 diabetes.

Cell Metab. 25, 1334-1347.e4 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The processes contributing to β cell dysfunction in type 2 diabetes (T2D) are uncertain, largely because it is difficult to access β cells in their intact immediate environment. We examined the pathophysiology of β cells under T2D progression directly in pancreatic tissues. We used MALDI imaging of Langerhans islets (LHIs) within mouse tissues or from human tissues to generate in situ-omics data, which we supported with in vitro experiments. Molecular interaction networks provided information on functional pathways and molecules. We found that stearoylcarnitine accumulated in β cells, leading to arrest of insulin synthesis and energy deficiency via excessive β-oxidation and depletion of TCA cycle and oxidative phosphorylation metabolites. Acetylcarnitine and an accumulation of N-acyl taurines, a group not previously detected in β cells, provoked insulin secretion. Thus, β cell dysfunction results from enhanced insulin secretion combined with an arrest of insulin synthesis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Langerhans Islets ; Maldi Imaging Mass Spectrometry ; Maldi-ft-icr ; N-acyl Taurines ; Acylcarnitines ; Diabetes Type 2 ; Pathophysiology ; β Cells; Imaging Mass-spectrometry; Metabolic-regulation; Glucose-tolerance; Pancreatic-islets; Resistance; Muscle; Mechanisms; Physiology; Expression; Obesity
Language english
Publication Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 1550-4131
e-ISSN 1932-7420
Journal Cell Metabolism
Quellenangaben Volume: 25, Issue: 6, Pages: 1334-1347.e4 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Cambridge
Reviewing status Peer reviewed
Institute(s) Research Unit Analytical Pathology (AAP)
Institute of Computational Biology (ICB)
Institute of Diabetes and Obesity (IDO)
Institute of Experimental Genetics (IEG)
CF Pathology & Tissue Analytics (CF-PTA)
POF-Topic(s) 30205 - Bioengineering and Digital Health
30201 - Metabolic Health
90000 - German Center for Diabetes Research
30505 - New Technologies for Biomedical Discoveries
Research field(s) Enabling and Novel Technologies
Helmholtz Diabetes Center
Genetics and Epidemiology
PSP Element(s) G-500390-001
G-554100-001
G-503800-001
G-502200-001
G-500600-001
G-501900-063
G-501900-062
A-630600-001
DOI 10.1016/j.cmet.2017.04.012
WOS ID WOS:000402961500013
Scopus ID 85020477611
PubMed ID 28591636
Erfassungsdatum 2017-06-13
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