N-acyl Taurines and Acylcarnitines Cause an Imbalance in Insulin Synthesis and Secretion Provoking beta Cell Dysfunction in Type 2 Diabetes

作者：Aichler Michaela^*; Borgmann Daniela; Krumsiek Jan; Buck Achim; MacDonald Patrick E; Fox Jocelyn E Manning; Lyon James; Light Peter E; Keipert Susanne; Jastroch Martin; Feuchtinger Annette; Mueller Nikola S; Sun Na; Palmer Andrew; Alexandrov Theodore; de Angelis Martin Hrabe; Neschen Susanne; Tschop Matthias H; Walch Axel^*

来源：Cell Metabolism, 2017, 25(6): 1334-+.

DOI：10.1016/j.cmet.2017.04.012

The processes contributing to beta cell dysfunction in type 2 diabetes (T2D) are uncertain, largely because it is difficult to access beta cells in their intact immediate environment. We examined the pathophysiology of b cells under T2D progression directly in pancreatic tissues. Weused 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 beta cells, leading to arrest of insulin synthesis and energy deficiency via excessive beta-oxidation and depletion of TCA cycle and oxidative phosphorylation metabolites. Acetylcarnitine and an accumulation of N-acyl taurines, a group not previously detected in beta cells, provoked insulin secretion. Thus, beta cell dysfunction results from enhanced insulin secretion combined with an arrest of insulin synthesis.

• 出版日期2017-6-6