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

Abstract

Diabetes mellitus (DM) is the most common chronic metabolic disease. Parkinson's disease (PD) is considered one of the most common neurodegenerative diseases. There are many similarities between both conditions. Both disorders are chronic diseases. Both diseases result from a decrease in a specific substance: dopamine in PD, and insulin in DM. Besides, both disorders arise due to the destruction of particular cells, dopaminergic cells in PD, and pancreatic beta-cell in DM. Recently, many epidemiological and experimental studies showed a connection between DM and PD. There are common underlying mechanisms in the pathophysiology of both diseases. These underlying mechanisms include mitochondrial dysfunction, oxidative stress, hyperglycemia, and inflammation. Insulin resistance is indeed the hallmark of DM, especially type 2 diabetes mellitus (T2DM), which plays a significant role in these pathophysiological and molecular mechanisms. Besides, many studies revealed that antidiabetic drugs have a beneficial effect on PD. In this current literature review, we aim to explore the standard pathophysiological and molecular linkages between these two disorders as well as how DM could affect the incidence and progression of PD. We also review how anti-diabetic drugs impact PD. In the future, further experimental and expanded clinical studies are needed to fully understand the exact pathophysiological connections between the two disorders and the efficacy of insulin and other anti-diabetic drugs in the treatment of PD in diabetic patients. Fully understanding and targeting these pathophysiological and molecular links could result in de novo curative therapy for PD and DM.

Targeted Ablation of Primary Cilia in Differentiated Dopaminergic Neurons Reduces Striatal Dopamine and Responsiveness to Metabolic Stress

“…In addition, previous data based on systemic glucose injections in rats also show an inhibitory effect on the firing of SN DA neurons [ 6 ]. Type II diabetes characterized by increased blood glucose and insulin resistance seems to increase the risk to develop Parkinson’s disease (PD), an age-related neurodegenerative disease in which SN DA neurons are progressively lost [ 7 , 8 ]. Several studies indicate a ciliary role in the function of the dopamine system.…”

MicroRNAs, Parkinson’s Disease, and Diabetes Mellitus

“…In addition to discussing the link of PD and DM through their common miRNA biomarkers, many studies revealed common underlying mechanisms in the pathophysiology of both diseases including hyperglycemia, mitochondrial dysfunction, oxidative stress, and inflammation [ 186 ]. PD results mainly from the death of dopaminergic neurons in the substantia nigra.…”

“…Oxidative stress results from an imbalance between harmful reactive oxygen species (ROS) and the antioxidant process that can lead to dopaminergic cell damage in PD as well as pancreatic β cell damage in DM. miRNAs can regulate ROS and prevent ROS-mediated damage to dopaminergic neurons [ 186 ]. Studies have focused on how to reduce the damage induced by oxidative stress in both PD and DM.…”

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 ].…”