INS and Parkinson disease: Moreover, in the substantia nigra pars compacta of patients with PD, death of dopaminergic neurons is often anticipated by marked loss of IR mRNA and enhanced levels of IRS phosphorylation at serine residues, with inhibitory action on insulin signaling and subsequent increased insulin resistance (Moroo et al., 1994; Takahashi et al., 1996; Duarte et al., 2012; Morris et al., 2014).