Making use of in vitro, in vivo, and ex vivo diabetic and IR-associated PD models, the present proof-of-concept study investigated if, to what extent, and how impaired insulin signaling contributes to the development and progression of PD; determined the likelihood and nature of association between mitochondrial function and altered SNCA expression; and explored for probable therapeutic exploitability of such molecular cross-talks in patients with PD. The gene discussed is INS; the disease is Parkinson disease.