Effects of metformin on learning and memory behaviors and brain mitochondrial functions in high fat diet induced insulin resistant rats

Pintana, Hiranya; Apaijai, Nattayaporn; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C.

doi:10.1016/j.lfs.2012.08.017

Cited by 213 publications

(140 citation statements)

References 48 publications

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“…These findings are consistent with our previous evidence showing that 12 weeks of HFD consumption in rats caused brain mitochondrial dysfunction (Pipatpiboon et al 2012). Previous studies as well as our findings suggest that the cognitive impairment caused by long-term HFD consumption could be related to brain mitochondrial dysfunction and oxidative stress , Stranahan et al 2008, White et al 2009, Pintana et al 2012. Interestingly, we found that both vildagliptin and sitagliptin completely restored brain mitochondrial function and improved learning and memory behaviors in rats with HFD-induced insulin resistance.…”

Section: Discussionsupporting

confidence: 93%

DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats

Pintana

Apaijai²,

Chattipakorn³

2013

Journal of Endocrinology

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172

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Recent evidence has demonstrated that insulin resistance is related to the development of type 2 diabetes mellitus. Our previous study found that high-fat diet (HFD) consumption caused not only peripheral and brain insulin resistance but also brain mitochondrial dysfunction and cognitive impairment. Vildagliptin and sitagliptin, dipeptidyl-peptidase-4 inhibitors, are recently developed anti-diabetic drugs. However, the effects of both drugs on cognitive behaviors and brain mitochondrial function in HFD-induced insulin-resistant rats have not yet been investigated. Sixty male Wistar rats were divided into two groups to receive either normal diet or HFD for 12 weeks. Rats in each group were then further divided into three treatment groups to receive either vehicle, vildagliptin (3 mg/kg per day), or sitagliptin (30 mg/kg per day) for 21 days. The cognitive behaviors of the rats were tested using the Morris Water Maze test. Blood samples were collected to determine metabolic parameters and plasma oxidative stress levels. Upon completion of the study, the animals were killed and the brains were removed to investigate brain and hippocampal mitochondrial function as well as to determine oxidative stress levels. We demonstrated that both drugs significantly improved the metabolic parameters and decreased circulating and brain oxidative stress levels in HFD-induced insulin-resistant rats. In addition, both drugs completely prevented brain and hippocampal mitochondrial dysfunction and equally improved the learning behaviors impaired by the HFD. Our findings suggest that the inhibition of dipeptidyl-peptidase-4 enzymes with vildagliptin or sitagliptin in insulinresistant rats not only increases peripheral insulin sensitivity but also decreases brain dysfunction. Key Words" insulin resistance " high-fat diet " DDP-4 inhibitors " memory decline " brain mitochondrial dysfunction

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Section: Discussionsupporting

confidence: 93%

DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats

Pintana

Apaijai²,

Chattipakorn³

2013

Journal of Endocrinology

Self Cite

172

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“…Sustained hyperglycaemia has been shown to cause hippocampal degeneration [11]. Induction of diabetes resulted in a slight decrease in hippocampal size, although not significant it may be of biological significance, especially since memory deficits were observed.…”

Section: Discussionmentioning

confidence: 99%

“…For these reasons, the intense metabolic control particularly by insulin has been shown to be effective in delaying the impairment of cognitive function in diabetes [10]. In the past, it has become apparent that insulin modulate some central nervous system functions [11]. In addition to the presence of metabolic derangements that result from hyperglycaemia, the lack of insulin has been associated with detrimental effects on cognitive function [11].…”

Section: Introductionmentioning

confidence: 99%

“…In the past, it has become apparent that insulin modulate some central nervous system functions [11]. In addition to the presence of metabolic derangements that result from hyperglycaemia, the lack of insulin has been associated with detrimental effects on cognitive function [11]. Insulin receptor signalling is vital for neurotransmitter synthesis and release through the increase in calcium and amino acids uptake [12].…”

Section: Introductionmentioning

confidence: 99%

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The Application of Pectin-Insulin Patch on Streptozotocin-Induced Diabetic Rats: Implications in the Hippocampal Function

Sibiya¹,

Mabandla²

2017

J Diabetes Metab

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Background: Diabetics are at high risk of developing dementia associated diseases compared to non-diabetics. The learning and memory impairments manifested in diabetes are attributed to sustained hyperglycaemia. Insulin injections are beneficial in preventing and attenuating the progression of these impairments. However, undesirable effects associated with the current mode of administration remains a challenge. In this study, we evaluated the effects of pectin-insulin patch on learning and memory deficits in diabetic animals.

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“…There was also an improvement in catalepsy, and the authors postulated that this was due, at least in part, to a reduction in oxidative stress induced by the treatment [79]. The neuroprotective effects of Metformin were also evaluated in vivo using high fat diet fed mice [80]. In this model, improving glycemic control following treatment with metformin was associated with a decrease in plasma oxidative stress, complete eradication of brain oxidative stress, improvement in mitochondrial dysfunction and protection against mitochondrial swelling [80].…”

Section: Metforminmentioning

confidence: 99%

Parkinson';s Disease, Diabetes and Cognitive Impairment

Ashraghi¹,

Pagano²,

Polychronis³

et al. 2016

EMI

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Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. Conclusion:Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

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Effects of metformin on learning and memory behaviors and brain mitochondrial functions in high fat diet induced insulin resistant rats

Cited by 213 publications

References 48 publications

DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats

DPP-4 inhibitors improve cognition and brain mitochondrial function of insulin-resistant rats

The Application of Pectin-Insulin Patch on Streptozotocin-Induced Diabetic Rats: Implications in the Hippocampal Function

Parkinson';s Disease, Diabetes and Cognitive Impairment

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