Evaluation of type 1 diabetes mellitus as a risk factor of Parkinson's disease in a Drosophila model

Abstract

Diabetes mellitus (DM) is a chronic metabolic disease characterized by high blood glucose levels, resulting from insulin dysregulation. Parkinson's disease (PD) is the most common neurodegenerative motor disorder caused by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta. DM and PD are both age‐associated diseases that are turning into epidemics worldwide. Previous studies have indicated that type 2 DM might be a risk factor of developing PD. However, scarce information about the link between type 1 DM (T1DM) and PD does exist. In this work, we have generated a Drosophila model of T1DM based on insulin deficiency to evaluate if T1DM could be a risk factor to trigger PD onset. As expected, model flies exhibited T1DM‐related phenotypes such as insulin deficiency, increased content of carbohydrates and glycogen, and reduced activity of insulin signaling. Interestingly, our results also demonstrated that T1DM model flies presented locomotor defects as well as reduced levels of tyrosine hydroxylase (a marker of DA neurons) in brains, which are typical PD‐related phenotypes. In addition, T1DM model flies showed elevated oxidative stress levels, which could be causative of DA neurodegeneration. Therefore, our results indicate that T1DM might be a risk factor of developing PD, and encourage further studies to shed light into the exact link between both diseases.

Causal relationships between type 1 diabetes mellitus and Alzheimer’s disease and Parkinson’s disease: a bidirectional two-sample Mendelian randomization study

“…This methodology represents an advancement over previous research methods, enhancing the reliability of the conclusions. A drosophila model of T1DM has shown reduced levels of tyrosine hydroxylase in the brain, a typical PD-related phenotype [ 8 ], suggesting that T1DM might be a risk factor for developing PD. On the other hand, compared to T1DM, T2MD model may be more associated with PD and has been demonstrated that more suitable for studying metabolic disturbance, which acts an early risk factor for PD [ 31 ].…”

“…T1DM has been postulated to expedite cognitive decline [ 6 ],with reports of elevated levels of phosphorylated Tau protein in T1DM patients [ 7 ], a factor associated with increased intracellular neurofibrillary tangle (NFT) formation in AD [ 6 ]. Furthermore, prior research has suggested that T1DM might act as a predisposing factor for PD [ 8 ].…”

Association between Type 1 Diabetes Mellitus and Parkinson’s Disease: A Mendelian Randomization Study

“…Interestingly, Sanz et al [35] generated a Drosophila model of T1DM based on insulin deficiency and found that these flies displayed insulin deficiency, increased levels of carbohydrates and glycogen, and reduced activity of insulin signaling, which are features of T1DM. These flies developed motor defects, reduced tyrosine hydroxylase (seen in dopamine neurons), and increased oxidative stress in their brains, mirroring the pathophysiology of PD in humans.…”