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Type 2 Diabetes (T2D) is associated with a state of low-grade inflammation that leads to insulin resistance under sustained high fat and glucose (HFG) stress.Mitochondria from pancreatic beta cells plays an essential role by metabolizing nutrients and generating signals required for both triggering and amplifying pathways of insulin secretion respond to HFG.However,the underlying pathway linking mitochondrial function to initiate and integrate inflammatory responses within the pancreatic beta cells under HFG stress remains poorly defined.Here,we demonstrated that HFG induced Ca2+ mediated deleterious effects on mitochondrial rho GTPase 1 (Miro1),a protein allowing mitochondria to move along microtubules to regulate mitochondria dynamics.