We are very happy to annouce the publication of a study led by Prof. Charna Dibner (Associate Professor in the Department of Surgery and Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva), Dr. Vlad Petrenko and Dr. Flore Sinturel investigating the link between circadian clocks and lipid homeostasis in pancreatic islets.
This study presents a temporal lipidomic profiling performed in human pancreatic islets isolated from 10 nondiabetic (ND) and 6 T2D donors. About 5% of the lipid metabolites across all major lipid classes exhibited pronounced circadian oscillations in ND human islets synchronized in vitro. Two-time point-based lipidomic analyses in T2D human islets revealed global and temporal alterations in phospho- and sphingolipids. Key enzymes regulating turnover of sphingolipids were rhythmically expressed in ND islets and exhibited altered levels in ND islets bearing disrupted clocks and in T2D islets. Strikingly, cellular membrane fluidity, measured by a Nile Red derivative NR12S, was reduced in plasma membrane of T2D diabetic human islets, in ND donors’ islets with disrupted circadian clockwork, or treated with sphingolipid pathway modulators. Moreover, inhibiting the glycosphingolipid biosynthesis led to strong reduction of insulin secretion triggered by glucose or KCl, whereas inhibiting earlier steps of de novo ceramide synthesis resulted in milder inhibitory effect on insulin secretion by ND islets. These data suggest that circadian clocks operative in human pancreatic islets are required for temporal orchestration of lipid homeostasis, and that perturbation of temporal regulation of the islet lipid metabolism upon T2D leads to altered insulin secretion and membrane fluidity.
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Plos Biology Aug 3;20(8):e3001725. (2022)
DOI information: 10.1371/journal.pbio.3001725