The Causal Role of Mitochondrial Dynamics in Regulating Insulin Resistance in Diabetes: Link through Mitochondrial Reactive Oxygen Species

Figure 7

Graphic summary delineates the causal role of mitochondrial dynamics in regulating insulin resistance of diabetes through mtROS. (1-2) Diabetes-susceptible haplogroup B4 demonstrates increased mtROS expression. (3-4) Increased mtROS contributes to insulin resistance and imbalanced profile of mitochondrial dynamics: enhanced fission proteins (Drp1 and Fis1) and reduced fusion proteins (Mfn1 and Mfn2), which ultimately contributes to mitochondrial fission (Kuo et al., 2016; Weng et al., 2013). (5–7) Mitochondrial fission inhibits insulin-activated IRS1-AKT signaling, which subsequently hinders GLUTs from translocating to cellular membrane and leads to insulin resistance. (8) Either genetic manipulation or pharmacological intervention effectively (9) correct mitochondrial dynamics toward a profile of fusion and simultaneously suppresses mtROS expression, which (10) boost insulin-activated IRS1-AKT signaling, and consequently (11) activates GLUTs translocation to cellular membrane and finally (12) improving insulin resistance.