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

Max Borsche; Andre Märtens; Philipp Hörmann; Theresa Brückmann; Katja Lohmann; Sinem Tunc; Christine Klein; Karsten Hiller; Alexander Balck

doi:10.1002/mds.29333

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

Max Borsche, Andre Märtens, Philipp Hörmann, Theresa Brückmann, Katja Lohmann, Sinem Tunc, Christine Klein, Karsten Hiller, Alexander Balck^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Technische Universität Braunschweig

9 Zitate (Scopus)

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.

Originalsprache	Englisch
Zeitschrift	Movement Disorders
Jahrgang	38
Ausgabenummer	4
Seiten (von - bis)	697-702
Seitenumfang	6
ISSN	0885-3185
DOIs	https://doi.org/10.1002/mds.29333
Publikationsstatus	Veröffentlicht - 04.2023

Fördermittel

The Michael J. Fox Foundation funded this project under the Spring 2018 Mitochondrial Biomarkers for Parkinson's Disease Initiative. This project was supported by SysMedPD (European Union's Horizon 2020 research and innovation program under Grant Agreement 668738), intramural grants from the University of Lübeck, and the State of Niedersachsen (Nierders. Vorab, Verbundvorhaben: “HOMEO‐HIRN,” ZN3673). Funding agencies: M.B. reports employment with University of Lübeck and University Hospital Schleswig‐Holstein Campus Lübeck and honoraria from Ipsen Pharma. A.M. reports employment withTU Braunschweig. P.H. reports employment with TU Braunschweig at the time of the study and current employment with agap2. T.B. reports employment with SANA Klinik Lübeck. K.L. reports employment with the University of Lübeck; honoraria from Springer; and grants from the German Research Foundation (DFG), Movement Disorders Society (MDS), Damp Foundation, and The Michael J. Fox Foundation (MJFF, GP2 project). S.T. reports employment with University of Lübeck and University Hospital Schleswig‐Holstein Campus Lübeck at the time of the study and current employment at a medical practice. C.K. reports consultancies with Centogene and Lundbeck; employment with University of Lübeck and University Hospital Schleswig‐Holstein Campus Lübeck; honoraria from Desitin and Bial; royalties from Oxford University Press; and grants from the German Research Foundation (DFG), The Michael J. Fox Foundation (MJFF), and Aligning Science Across Parkinson's (ASAP). K.H. reports employment with TU Braunschweig and grants from German Research Foundation (DFG), German Federal Ministry of Education and Research (BMBF), Lower Saxony Ministry of Science and Culture (MWK), and Technical University Braunschweig. A.B. reports stock ownership in Sartorius AG, employment with University of Lübeck and University Hospital Schleswig‐Holstein Campus Lübeck, a German Research Foundation (DFG) stipend for a research stay in Leiden, the Netherlands, and intramural funds of the University of Lübeck.

Träger	Trägernummer
State of Niedersachsen	ZN3673
Michael J. Fox Foundation for Parkinson's Research
International Parkinson and Movement Disorder Society
Niedersächsische Ministerium für Wissenschaft und Kultur
Aligning Science Across Parkinson’s
Deutsche Forschungsgemeinschaft
Bundesministerium für Bildung und Forschung
Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg
Horizon 2020	668738
Damp Stiftung

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)
Querschnittsbereich: Medizinische Genetik

DFG-Fachsystematik

2.23-06 Molekulare und zelluläre Neurologie und Neuropathologie

Dokumente

10.1002/mds.29333

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title = "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.",

author = "Max Borsche and Andre M{\"a}rtens and Philipp H{\"o}rmann and Theresa Br{\"u}ckmann and Katja Lohmann and Sinem Tunc and Christine Klein and Karsten Hiller and Alexander Balck",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",

year = "2023",

month = apr,

doi = "10.1002/mds.29333",

language = "English",

volume = "38",

pages = "697--702",

journal = "Movement Disorders",

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T1 - In Vivo Investigation of Glucose Metabolism in Idiopathic and PRKN-Related Parkinson's Disease

AU - Borsche, Max

AU - Märtens, Andre

AU - Hörmann, Philipp

AU - Brückmann, Theresa

AU - Lohmann, Katja

AU - Tunc, Sinem

AU - Klein, Christine

AU - Hiller, Karsten

AU - Balck, Alexander

PY - 2023/4

Y1 - 2023/4

N2 - 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.

AB - 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.

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U2 - 10.1002/mds.29333

DO - 10.1002/mds.29333

M3 - Journal articles

C2 - 36717366

AN - SCOPUS:85147334620

SN - 0885-3185

VL - 38

SP - 697

EP - 702

JO - Movement Disorders

JF - Movement Disorders

IS - 4

ER -

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

Abstract

Fördermittel

UN SDGs

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

Dokumente

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