These changes in turn lead to the activation of c-Jun N-terminal kinase (JNK), thus inhibiting insulin receptor signaling, causing insulin resistance, metabolic dysfunction, cellular stress and inflammation, as well as mitochondrial degeneration and an increase in ROS secretion in cells, accompanied by defective glucose-stimulated insulin secretion.25 We also found that Smpd3 was downregulated in BMSCs of patients with diabetes with fluctuating blood glucose, which suggests that Smpd3 has potential research value in the pathological mechanism of T2DM. The gene discussed is INSR; the disease is Insulin resistance.