Diabetes and Parkinson disease

There are many superficial similarities between diabetes mellitus (DM) and Parkinson disease (PD). In both cases, clinical manifestations are primarily attributable to the decrement and then absence of a biological product (insulin and dopamine) with diminution and ultimately substantial or near-complete loss of cells in specialized tissue that produce the agent. The diseases affect multiple organ systems and can be treated by agonists and by replacement of the agent. Other options include stimulators, tissue transplants, and pumps. But deep down, there are biologically plausible cellular mechanisms that intertwine both of these conditions. Insulin receptors are relatively plentiful in substantia nigra neurons,¹ and hyperglycemia suppresses substantia nigra dopaminergic neuronal firing as well as decreases dopamine turnover. Attention has increasingly focused on mitochondria as a link between DM and PD. Insulin resistance has been associated with mitochondrial dysfunction, while MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a toxin that caused numerous cases of parkinsonism, leads to mitochondrial dysfunction. Insulin resistance is associated with decreased genetic expression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1 Alpha), a key regulator of mitochondrial genesis and functioning, with resultant organelle destruction (mitophagy), as well as increased oxidative stress and toxic mitochondrial mutations. Evidence suggests there may be diminished expression of PGC1 Alpha genes in PD as well.²