SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats

© 2017 Elsevier Inc. Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in...

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Main Authors: Sa-nguanmoo P., Tanajak P., Kerdphoo S., Jaiwongkam T., Pratchayasakul W., Chattipakorn N., Chattipakorn S.
Format: Journal
Published: 2017
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85027518734&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/40077
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spelling th-cmuir.6653943832-400772017-09-28T03:58:32Z SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats Sa-nguanmoo P. Tanajak P. Kerdphoo S. Jaiwongkam T. Pratchayasakul W. Chattipakorn N. Chattipakorn S. © 2017 Elsevier Inc. Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n = 8) or a high-fat diet (HFD, n = 32) for 16 weeks. At week 13, the HFD-fed rats were divided into four subgroups (n = 8/subgroup) to receive either a vehicle, vildagliptin (3 mg/kg/day) dapagliflozin (1 mg/kg/day) or combined drugs for four weeks. ND rats were given a vehicle for four weeks. Metabolic parameters and brain function were investigated. The results demonstrated that HFD rats developed obese-insulin resistance and cognitive decline. Dapagliflozin had greater efficacy on improved peripheral insulin sensitivity and reduced weight gain than vildagliptin. Single therapy resulted in equally improved brain mitochondrial function, insulin signaling, apoptosis and prevented cognitive decline. However, only dapagliflozin improved hippocampal synaptic plasticity. A combination of the drugs had greater efficacy in improving brain insulin sensitivity and reducing brain oxidative stress than the single drug therapy. These findings suggested that dapagliflozin and vildagliptin equally prevented cognitive decline in the obese-insulin resistance, possibly through some similar mechanisms. Dapagliflozin had greater efficacy than vildagliptin for preserving synaptic plasticity, thus combined drugs could be the best therapeutic approach for neuroprotection in the obese-insulin resistance. 2017-09-28T03:58:32Z 2017-09-28T03:58:32Z Journal 0041008X 2-s2.0-85027518734 10.1016/j.taap.2017.08.005 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85027518734&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/40077
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description © 2017 Elsevier Inc. Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n = 8) or a high-fat diet (HFD, n = 32) for 16 weeks. At week 13, the HFD-fed rats were divided into four subgroups (n = 8/subgroup) to receive either a vehicle, vildagliptin (3 mg/kg/day) dapagliflozin (1 mg/kg/day) or combined drugs for four weeks. ND rats were given a vehicle for four weeks. Metabolic parameters and brain function were investigated. The results demonstrated that HFD rats developed obese-insulin resistance and cognitive decline. Dapagliflozin had greater efficacy on improved peripheral insulin sensitivity and reduced weight gain than vildagliptin. Single therapy resulted in equally improved brain mitochondrial function, insulin signaling, apoptosis and prevented cognitive decline. However, only dapagliflozin improved hippocampal synaptic plasticity. A combination of the drugs had greater efficacy in improving brain insulin sensitivity and reducing brain oxidative stress than the single drug therapy. These findings suggested that dapagliflozin and vildagliptin equally prevented cognitive decline in the obese-insulin resistance, possibly through some similar mechanisms. Dapagliflozin had greater efficacy than vildagliptin for preserving synaptic plasticity, thus combined drugs could be the best therapeutic approach for neuroprotection in the obese-insulin resistance.
format Journal
author Sa-nguanmoo P.
Tanajak P.
Kerdphoo S.
Jaiwongkam T.
Pratchayasakul W.
Chattipakorn N.
Chattipakorn S.
spellingShingle Sa-nguanmoo P.
Tanajak P.
Kerdphoo S.
Jaiwongkam T.
Pratchayasakul W.
Chattipakorn N.
Chattipakorn S.
SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats
author_facet Sa-nguanmoo P.
Tanajak P.
Kerdphoo S.
Jaiwongkam T.
Pratchayasakul W.
Chattipakorn N.
Chattipakorn S.
author_sort Sa-nguanmoo P.
title SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats
title_short SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats
title_full SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats
title_fullStr SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats
title_full_unstemmed SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats
title_sort sglt2-inhibitor and dpp-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in hfd-induced obese rats
publishDate 2017
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85027518734&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/40077
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