Diabetes, a Contemporary Risk for Parkinson’s Disease: Epidemiological and Cellular Evidences

Abstract

Diabetes mellitus (DM), a group of diseases characterized by defective glucose metabolism, is the most widespread metabolic disorder affecting over 400 million adults worldwide. This pathological condition has been implicated in the pathogenesis of a number of central encephalopathies and peripheral neuropathies. In further support of this notion, recent epidemiological evidence suggests a link between DM and Parkinson’s disease (PD), with hyperglycemia emerging as one of the culprits in neurodegeneration involving the nigrostriatal pathway, the neuroanatomical substrate of the motor symptoms affecting parkinsonian patients. Indeed, dopaminergic neurons located in the mesencephalic substantia nigra appear to be particularly vulnerable to oxidative stress and degeneration, likely because of their intrinsic susceptibility to mitochondrial dysfunction, which may represent a direct consequence of hyperglycemia and hyperglycemia-induced oxidative stress. Other pathological pathways induced by increased intracellular glucose levels, including the polyol and the hexosamine pathway as well as the formation of advanced glycation end-products, may all play a pivotal role in mediating the detrimental effects of hyperglycemia on nigral dopaminergic neurons. In this review article, we will examine the epidemiological as well as the molecular and cellular clues supporting the potential susceptibility of nigrostriatal dopaminergic neurons to hyperglycemia.

Diabetes Mellitus and Parkinson's Disease: Shared Pathophysiological Links and Possible Therapeutic Implications

“…The motor manifestations include resting asymmetric tremors in the upper limbs, bradykinesia, gait difficulties. Non-motor symptoms include dementia, depression, social phobia, anxiety, loss of smell, fear, and autonomic symptoms [3]. The motor symptoms are related to the destruction of the pigmented neuronal cells in the substantia nigra (SN) in the brain; these are dopamine secreting cells.…”

Narcolepsy in Parkinson's disease with insulin resistance

“…By the time clinical signs of PD are identified and a diagnosis is made, a large number of dopaminergic neurons are already lost 1 . Dopaminergic neurons are also involved in promoting feeding behavior in the hypoglycemic state which is mediated by insulin receptors in the substantia nigra, indicating that dopaminergic neuronal loss may alter glycemic control 38,39 . Loss of orexin/hypocretin is also linked to binge-eating behavior, low BMR, and obesity, which is also a symptom of narcolepsy.…”

Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

“…Epidemiological evidence suggests a link between PD and T2D [ 35 , 36 , 37 , 38 , 39 , 302 ]. T2D is a negative prognostic factor associated with faster motor progression and cognitive decline in PD.…”

“…The data for PD and Alzheimer’s disease (AD) suggest that a number of insults occurring early in life may lead or contribute to both diseases [ 34 ]. Furthermore, strong epidemiological evidence suggests a link between PD and diabetes mellitus type 2 (T2D) [ 35 , 36 , 37 , 38 , 39 ].…”