INS and diabetes mellitus: Mechanistically, (1) inhibition of the AGE-RAGE pathway can alleviate hyperglycemia-induced inflammatory damage and insulin resistance [50]; (2) functional restoration of the PI3K-Akt pathway, a hub for insulin signal transduction, directly ameliorates glucose metabolism disorders [51]; (3) modulation of the HIF-1 pathway may mitigate diabetes-associated hypoxic stress [52].