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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)
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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
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