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

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

The processes contributing to ? cell dysfunction in type 2 diabetes (T2D) are uncertain, largely because it is difficult to access ? cells in their intact immediate environment. We examined the pathophysiology of ? 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...     »