Not only metformin, but also D-allulose, alleviates metabolic disturbance and cognitive decline in prediabetic rats

ABSTRACT

Background

Prediabetes can be characterized as obesity with metabolic disturbance, leading to cognitive decline and brain pathologies. D-allulose administration in obese animals decreased metabolic disturbance. However, the comparative effects of D-allulose and metformin on cognition and brain functions in the diet-induced prediabetic condition are unclear. We assume that both D-allulose and metformin equally restore cognition and brain functions in prediabetic rats to an equal extent.

Materials and methods

Fifty-six rats were randomly divided into two groups: a control and diet-induced prediabetic group which had received a normal diet (ND) and a high-fat diet (HFD) for 24 weeks, respectively. After dietary protocol had been followed for 12 weeks, ND rats were given solely drinking water daily for 12 weeks. HFD-prediabetic rats randomly received drinking water with either D-allulose (1.9 g/kg/day of D-allulose) or metformin (300 mg/kg/day of metformin) for 12 weeks. Following this, cognition and brain parameters were determined.

Results

Brain oxidative stress, mitochondrial dysfunction, microglial hyper-activation, apoptosis, brain insulin insensitivity, hippocampal synaptic dysfunction, and cognitive decline were observed in prediabetic rats. D-allulose and metformin equally attenuated brain oxidative stress, brain mitochondrial ROS production, hippocampal apoptosis, brain insulin insensitivity, hippocampal synaptic dysfunction, resulting in improved learning process in prediabetic rats. Metformin conferred greater advantage on the amelioration of brain mitochondrial dysfunction and brain microglial hyper-activation than D-allulose, resulting in improvement in both learning and memory processes in prediabetic rats.

Conclusions

Not only metformin, but also D-allulose, has beneficial effects on the enhancement of brain function and cognition in prediabetic condition.

KEYWORDS:

• D-allulose
• metformin
• diet-induced obesity
• brain function
• cognition
• brain mitochondrial dysfunction
• microglial hyper-activation
• brain apoptosis

Disclosure statement

This study was partly supported by a grant from the Research and Development Department, Matsutani Chemical Industry Company, Japan. However, they were not involved in any part of this study including the data collection, interpretation, and report in this manuscript.

Additional information

Funding

This work was supported by grants from the Research and Development Department, Matsutani Chemical Industry Company, and the Chiang Mai University Center of Excellence Award. WP is also supported by Thailand Research Fund awards (RSA6180071). NC is also supported by the Research Chair grant from the National Science and Technology Development Agency Thailand. SCC is supported by the Senior Research Scholar grant from the National Research Council of Thailand. All funders were not involved in the data collection, interpretation, and report in this manuscript.

Notes on contributors

Wasana Pratchayasakul

Wasana Pratchayasakul is an Associate Professor of Physiology at the Department of Physiology, Faculty of Medicine, Chiang Mai University; and is a staff of Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University.

Kewarin Jinawong

Kewarin Jinawong is a PhD student at the Department of Physiology, Faculty of Medicine, Chiang Mai University.

Wanpitak Pongkan

Wanpitak Pongkan is a lecturer at the Department of Veterinary Biosciences and Public Health, Faculty of Veterinary Medicine, Chiang Mai University.

Thidarat Jaiwongkam

Thidarat Jaiwongkama is a research technician at the Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University.

Busarin Arunsak

Busarin Arunsak is a research technician at the Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University.

Titikorn Chunchai

Titikorn Chunchai is a researcher at the Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University.

Masaaki Tokuda

Masaaki Tokuda is a Professor at the International Institute of Rare Sugar Research and Education, Kagawa University.

Nipon Chattipakorn

Nipon Chattipakorn is a Professor of Physiology at the Department of Physiology, Faculty of Medicine, Chiang Mai University; and is a Director of Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University.

Siriporn C. Chattipakorn

Siriporn C. Chattipakorn is a Professor of Neurophysiology and Oral Biology at the Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai, University; and is a Head of Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University.