Fenofibrate increases very-long-chain sphingolipids and improves blood glucose homeostasis in NOD mice.

摘要: Sphingolipid metabolism regulates beta cell biology and inflammation is abnormal at the onset of type 1 diabetes. Fenofibrate, a regulator sphingolipid metabolism, known to prevent diabetes in NOD mice. Here, we aimed investigate effects fenofibrate on pancreatic lipidome, pancreas morphology, sympathetic nerves blood glucose homeostasis We treated female mice with from 3 weeks age. The lipidome was analysed using MS. Analysis islet volume performed by stereology. Islet nerve fibre evaluated tyrosine hydroxylase staining. effect assessed measuring non-fasting age 12 30 weeks. Furthermore, measured tolerance, fasting insulin glucagon levels, tolerance. found that selectively increases amount very-long-chain sphingolipids In addition, causes remodelling an increased lysoglycerophospholipids. Fenofibrate did not affect or volume, but led higher fibres hydroxylase-positive cells. Fenofibrate-treated had more stable glucose, which associated reduced glucose. improved levels prevented hyperinsulinaemia. These data indicate alters anti-inflammatory anti-apoptotic state. beneficial could be used as therapeutic approach improve diabetes-associated pathologies.