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In vitro, in differentiated human DA neurons, IR was associated with increased -synuclein and ROS levels, as well as mitochondrial depolarization, which may be mediated by polo-like kinase-2.177 In vivo, mitochondrial dynamics-related factor Parkin was significantly reduced in the substantia nigra of a mice fed a high-fat diet and a diabetic mice, leading to the accumulation of Parkin-interacting substrate and the reduction of PGC-1.41 Also, high glucose levels may modulate Parkin/PINK1-mediated mitochondrial autophagy in DA cells through the thioredoxin-interacting protein.178 All the above mechanisms suggest that diabetes-related metabolic factors may promote PD by regulating the mitochondria

The reduction in systemic inflammation is likely a major contributor to the mood benefits

These small errors compound over weeks of dosing

Footnotes This article is part of a special issue entitled: Insulin Resistance, Diabetes and Metabolism published in Metabolism Open