In Vivo Investigation of Glucose Metabolism in Idiopathic and PRKN‐Related Parkinson's Disease

Abstract

Background Alterations in mitochondrial dysfunction have been implicated in the pathogenesis of Parkinson's disease (PD). Mitochondrial energy production is linked to glucose metabolism, and diabetes is associated with PD. However, studies investigating glucose metabolism in vivo in genetically stratified PD patients and controls have yet to be performed. Objectives The objectives of this study were to explore glucose production, gluconeogenesis, and the contribution of gluconeogenesis to glucose production in idiopathic and PRKN PD compared with healthy controls with state‐of‐the‐art biochemical methods. Methods We applied a dried‐blood sampling/gas chromatography/mass spectrometry approach to monitor fluxes in the Cori cycle in vivo. Results The contribution of gluconeogenesis to total glucose production is increased in idiopathic PD patients (n = 33), but not in biallelic PRKN mutation carriers (n = 5) compared with healthy controls (n = 13). Conclusions We provide first‐time in vivo evidence for alterations in glucose metabolism in idiopathic PD, in keeping with the epidemiological evidence for an association between PD and diabetes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The role of dopaminergic medication, lipid, and endocannabinoid pathway alterations in idiopathic andPRKN/PINK1-mediated Parkinson’s disease – a large-scale targeted metabolomics study

“…Accumulation of Citric acid, the starting point of the citric acid circle, could also indicate a shift from oxidative phosphorylation to increased glycolysis due to mitochondrial dysfunction, which we previously described. 53,54…”

“…Accumulation of Citric acid, the starting point of the citric acid circle, could also indicate a shift from oxidative phosphorylation to increased glycolysis due to mitochondrial dysfunction, which we previously described. 53,54 Mito-PD Only one study investigated the metabolome in PRKN-linked PD 55 and no investigations addressing patients with PINK1-linked PD have been available thus far. We combined these two autosomal recessively inherited forms of PD, as the proteins encoded by these genes act in a common biochemical pathway, mainly involved in the degradation of damaged mitochondria, 6 but also links to alterations of innate immune system have been described to be associated with Parkin and Pink1 dysfunction.…”

Identification of metabolites reproducibly associated with Parkinson’s Disease via meta-analysis and computational modelling

“…Energy dysfunction is highly related to the alterations in glucose metabolism in the pathogenesis of PD [115]. Increased levels of glucose [79,71,96] were identified in the blood and CSF of PD patients in three studies, while decreased levels [64,94] were identified in the plasma and CSF of PD patients in two studies.…”

Identification of Shared Pathogenetic Genes in Parkinson’s Disease and Type 2 Diabetes

“…The selective loss of dopaminergic neurons in the substantia nigra and abnormal accumulation of α-synuclein are typical pathological hallmarks of PD [1]. Mitochondrial dysfunction has been identified as an important mechanism in PD and is linked to glucose metabolism [2]. PD patients have alterations in glucose metabolism compared with healthy controls, such as increased glycolysis and gluconeogenesis [2,3].…”

“…Mitochondrial dysfunction has been identified as an important mechanism in PD and is linked to glucose metabolism [2]. PD patients have alterations in glucose metabolism compared with healthy controls, such as increased glycolysis and gluconeogenesis [2,3]. Furthermore, impaired brain glucose metabolism has been reported in neurodegenerative diseases, including Alzheimer's disease, PD, Huntington's disease, and frontotemporal dementia [4][5][6][7].…”