Mitofusins Mfn1 and Mfn2 are required to preserve glucose-but not incretin- stimulated beta cell connectivity and insulin secretion

Aims/hypothesis: Mitochondrial glucose metabolism is essential for stimulated insulin release from pancreatic beta cells. Whether mitochondrial networks may be important for glucose or incretin sensing has yet to be determined. Methods: Here, we generated mice with beta cell-selective, adult-restricted deletion of the mitofusin genes Mfn1 and Mfn2 (βMfn1/2 dKO). Whole or dissociated pancreatic islets were used for live beta cell fluorescence imaging of cytosolic or mitochondrial Ca2+ concentration and ATP production or GSIS in response to increasing glucose concentrations or GLP-1 receptor agonists. Serum and blood samples were collected to examine oral and i.p. glucose tolerance. Results: βMfn1/2 dKO mice displayed elevated fed and fasted glycaemia (p five-fold decrease (p