IMPACT OF MFN2 DELETION ON INSULIN SECRETION AND TRANSIENT MITOCHONDRIAL PERMEABILITY TRANSITION PORE OPENING IN HUMAN ENDOCBH3 BETA CELLS

Abstract

Mitofusins are membrane-bound GTPases responsible for the fusion of mitochondria in mammalian cells and, thus, the maintenance of an interconnected mitochondrial network. Correspondingly, mutations in human MFN2 are associated with lipodystrophies and increased diabetes risk. Our group has recently reported that deleting the mouse homologues Mfn1 and Mfn2 selectively in the beta cell results in mitochondrial fragmentation, severely impaired insulin secretion, and hyperglycemia (Georgiadou et al, Diabetes, 2022). The latter is partly reversed by treatment with glucagon-like peptide-1 receptor (GLP1R) agonists, such as exednin-4 (Ex4). Whether these findings also apply to human beta cells has been unclear up to now.