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Hyperpolarized [1-13C]pyruvate Magnetic Resonance Spectroscopy Shows That Agmatine Increased Lactate Production in the Brain of Type 2 Diabetic Mice

Authors
 Young-Suk Choi  ;  Jae Eun Song  ;  Eosu Kim  ;  Chul Hoon Kim  ;  Jong Eun Lee  ;  Ho-Taek Song 
Citation
 YONSEI MEDICAL JOURNAL, Vol.64(10) : 625-632, 2023-10 
Journal Title
YONSEI MEDICAL JOURNAL
ISSN
 0513-5796 
Issue Date
2023-10
MeSH
Agmatine* ; Animals ; Brain ; Diabetes Mellitus, Experimental* ; Diabetes Mellitus, Type 2* ; Lactic Acid ; Mice ; Mice, Inbred ICR ; NAD ; Pyruvic Acid
Keywords
Alzheimer's disease ; agmatine ; hyperpolarized 13C ; lactate ; magnetic resonance spectroscopy
Abstract
Purpose: Type 2 diabetes mellitus (T2DM) is associated with a 2-fold increased risk of developing Alzheimer's disease. In earlier research, agmatine has been demonstrated to alleviate diabetes symptoms and increase cognitive performance. However, it is unclear whether the improvement of cognitive function is attributable to the reduction of diabetic symptoms or its direct influence on brain metabolism. Using hyperpolarized (HP) [1-13C]pyruvate magnetic resonance spectroscopy (MRS), this study intends to evaluate the influence of agmatine on brain metabolism.

Materials and methods: ICR mice were fed a high-fat diet and injected with streptozotocin to develop a T2DM animal model. During a 2-week period, T2DM mice were treated with normal saline or 100 mg/kg of agmatine, and brain HP [1-13C]pyruvate MRS was performed. The effect of agmatine on lactate generation and NADH/NAD+ redox state was investigated using C6 and neuro-2a (N2a) cells.

Results: As a perfusion marker, the total 13C signals in the brain of T2DM mice (p=0.07) and agmatine-treated mice (p<0.05) were reduced. The conversion constant (Kpl) from [1-13C]pyruvate to [1-13C]lactate was not distinguishable in the brains of T2DM mice but was significantly increased in the brains of agmatine-treated T2DM mice. Treating C6 and N2a cells with agmatine increased NADH/NAD+ratio and lactate generation.

Conclusion: Agmatine influences the NADH/NAD+ redox state in the brains of T2DM mice, which may be connected with enhanced cognitive performance and increased conversion of HP [1-13C]pyruvate to HP [1-13C]lactate.
Files in This Item:
T202305852.pdf Download
DOI
10.3349/ymj.2022.0554
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Psychiatry (정신과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eosu(김어수) ORCID logo https://orcid.org/0000-0001-9472-9465
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Song, Ho Taek(송호택) ORCID logo https://orcid.org/0000-0002-6655-2575
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
Choi, Young Suk(최영숙) ORCID logo https://orcid.org/0000-0003-4930-8455
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/196552
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