GLP-1 analog liraglutide protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats

Tomoaki Inoue, Toyoshi Inoguchi, Noriyuki Sonoda, Hari Hendarto, Hiroaki Makimura, Shuji Sasaki, Hisashi Yokomizo, Yoshinori Fujimura, Daisuke Miura, Ryoichi Takayanagi

研究成果: ジャーナルへの寄稿記事

40 引用 (Scopus)

抄録

Objective: Accumulating evidence has implicated that GLP-1 may have a beneficial effect on cardiovascular but the mechanism is not fully understood. Here we show that GLP-1 analog, liraglutide, inhibits cardiac steatosis, oxidative stress and apoptosis in streptozotocin (STZ)-induced type 1 diabetic rats, via activation of AMPK-Sirt1 pathway. Methods: Diabetic rats were treated with subcutaneous injections of liraglutide (0.3mg/kg/12h) for 4 weeks. Myocardial steatosis (detected by oil red O staining and myocardial triglyceride and diacylglycerol (DAG) contents assay), expression of protein kinase C (PKC), heart NAD(P)H oxidase activity, oxidative stress markers (8-hydroxy-2'-deoxyguanosine staining), apoptosis (TUNEL analysis) and genes that affect apoptosis and lipid metabolism were evaluated. Results: Administration of liraglutide did not affect plasma glucose and insulin levels or body weights in STZ-induced diabetic rats, but normalized myocardial steatosis, expression of PKC, NAD(P)H oxidase activity, oxidative stress markers and apoptosis, all of which were significantly increased in diabetic hearts. Additionally, expression of genes mediating lipid uptake, synthesis and oxidation were increased in the diabetic hearts, and these increases were all reduced by liraglutide. In addition, liraglutide increased expression of Sirt1 and phosphorylated AMPK in the diabetic hearts. Conclusions: Liraglutide may have a beneficial effect on cardiac steatosis, DAG-PKC-NAD(P)H pathway, oxidative stress and apoptosis via activation of AMPK-Sirt1 pathway, independently of a glucose-lowering effect.

元の言語英語
ページ(範囲)250-259
ページ数10
ジャーナルAtherosclerosis
240
発行部数1
DOI
出版物ステータス出版済み - 5 1 2015

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Glucagon-Like Peptide 1
Streptozocin
Oxidative Stress
Apoptosis
AMP-Activated Protein Kinases
Protein Kinase C
NADPH Oxidase
Diacylglycerol Kinase
Staining and Labeling
Glucose
Diglycerides
In Situ Nick-End Labeling
Subcutaneous Injections
Lipid Metabolism
NAD
Liraglutide
Triglycerides
Body Weight
Insulin
Lipids

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

これを引用

GLP-1 analog liraglutide protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats. / Inoue, Tomoaki; Inoguchi, Toyoshi; Sonoda, Noriyuki; Hendarto, Hari; Makimura, Hiroaki; Sasaki, Shuji; Yokomizo, Hisashi; Fujimura, Yoshinori; Miura, Daisuke; Takayanagi, Ryoichi.

:: Atherosclerosis, 巻 240, 番号 1, 01.05.2015, p. 250-259.

研究成果: ジャーナルへの寄稿記事

Inoue, T, Inoguchi, T, Sonoda, N, Hendarto, H, Makimura, H, Sasaki, S, Yokomizo, H, Fujimura, Y, Miura, D & Takayanagi, R 2015, 'GLP-1 analog liraglutide protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats', Atherosclerosis, 巻. 240, 番号 1, pp. 250-259. https://doi.org/10.1016/j.atherosclerosis.2015.03.026
Inoue, Tomoaki ; Inoguchi, Toyoshi ; Sonoda, Noriyuki ; Hendarto, Hari ; Makimura, Hiroaki ; Sasaki, Shuji ; Yokomizo, Hisashi ; Fujimura, Yoshinori ; Miura, Daisuke ; Takayanagi, Ryoichi. / GLP-1 analog liraglutide protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats. :: Atherosclerosis. 2015 ; 巻 240, 番号 1. pp. 250-259.
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abstract = "Objective: Accumulating evidence has implicated that GLP-1 may have a beneficial effect on cardiovascular but the mechanism is not fully understood. Here we show that GLP-1 analog, liraglutide, inhibits cardiac steatosis, oxidative stress and apoptosis in streptozotocin (STZ)-induced type 1 diabetic rats, via activation of AMPK-Sirt1 pathway. Methods: Diabetic rats were treated with subcutaneous injections of liraglutide (0.3mg/kg/12h) for 4 weeks. Myocardial steatosis (detected by oil red O staining and myocardial triglyceride and diacylglycerol (DAG) contents assay), expression of protein kinase C (PKC), heart NAD(P)H oxidase activity, oxidative stress markers (8-hydroxy-2'-deoxyguanosine staining), apoptosis (TUNEL analysis) and genes that affect apoptosis and lipid metabolism were evaluated. Results: Administration of liraglutide did not affect plasma glucose and insulin levels or body weights in STZ-induced diabetic rats, but normalized myocardial steatosis, expression of PKC, NAD(P)H oxidase activity, oxidative stress markers and apoptosis, all of which were significantly increased in diabetic hearts. Additionally, expression of genes mediating lipid uptake, synthesis and oxidation were increased in the diabetic hearts, and these increases were all reduced by liraglutide. In addition, liraglutide increased expression of Sirt1 and phosphorylated AMPK in the diabetic hearts. Conclusions: Liraglutide may have a beneficial effect on cardiac steatosis, DAG-PKC-NAD(P)H pathway, oxidative stress and apoptosis via activation of AMPK-Sirt1 pathway, independently of a glucose-lowering effect.",
author = "Tomoaki Inoue and Toyoshi Inoguchi and Noriyuki Sonoda and Hari Hendarto and Hiroaki Makimura and Shuji Sasaki and Hisashi Yokomizo and Yoshinori Fujimura and Daisuke Miura and Ryoichi Takayanagi",
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T1 - GLP-1 analog liraglutide protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats

AU - Inoue, Tomoaki

AU - Inoguchi, Toyoshi

AU - Sonoda, Noriyuki

AU - Hendarto, Hari

AU - Makimura, Hiroaki

AU - Sasaki, Shuji

AU - Yokomizo, Hisashi

AU - Fujimura, Yoshinori

AU - Miura, Daisuke

AU - Takayanagi, Ryoichi

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Objective: Accumulating evidence has implicated that GLP-1 may have a beneficial effect on cardiovascular but the mechanism is not fully understood. Here we show that GLP-1 analog, liraglutide, inhibits cardiac steatosis, oxidative stress and apoptosis in streptozotocin (STZ)-induced type 1 diabetic rats, via activation of AMPK-Sirt1 pathway. Methods: Diabetic rats were treated with subcutaneous injections of liraglutide (0.3mg/kg/12h) for 4 weeks. Myocardial steatosis (detected by oil red O staining and myocardial triglyceride and diacylglycerol (DAG) contents assay), expression of protein kinase C (PKC), heart NAD(P)H oxidase activity, oxidative stress markers (8-hydroxy-2'-deoxyguanosine staining), apoptosis (TUNEL analysis) and genes that affect apoptosis and lipid metabolism were evaluated. Results: Administration of liraglutide did not affect plasma glucose and insulin levels or body weights in STZ-induced diabetic rats, but normalized myocardial steatosis, expression of PKC, NAD(P)H oxidase activity, oxidative stress markers and apoptosis, all of which were significantly increased in diabetic hearts. Additionally, expression of genes mediating lipid uptake, synthesis and oxidation were increased in the diabetic hearts, and these increases were all reduced by liraglutide. In addition, liraglutide increased expression of Sirt1 and phosphorylated AMPK in the diabetic hearts. Conclusions: Liraglutide may have a beneficial effect on cardiac steatosis, DAG-PKC-NAD(P)H pathway, oxidative stress and apoptosis via activation of AMPK-Sirt1 pathway, independently of a glucose-lowering effect.

AB - Objective: Accumulating evidence has implicated that GLP-1 may have a beneficial effect on cardiovascular but the mechanism is not fully understood. Here we show that GLP-1 analog, liraglutide, inhibits cardiac steatosis, oxidative stress and apoptosis in streptozotocin (STZ)-induced type 1 diabetic rats, via activation of AMPK-Sirt1 pathway. Methods: Diabetic rats were treated with subcutaneous injections of liraglutide (0.3mg/kg/12h) for 4 weeks. Myocardial steatosis (detected by oil red O staining and myocardial triglyceride and diacylglycerol (DAG) contents assay), expression of protein kinase C (PKC), heart NAD(P)H oxidase activity, oxidative stress markers (8-hydroxy-2'-deoxyguanosine staining), apoptosis (TUNEL analysis) and genes that affect apoptosis and lipid metabolism were evaluated. Results: Administration of liraglutide did not affect plasma glucose and insulin levels or body weights in STZ-induced diabetic rats, but normalized myocardial steatosis, expression of PKC, NAD(P)H oxidase activity, oxidative stress markers and apoptosis, all of which were significantly increased in diabetic hearts. Additionally, expression of genes mediating lipid uptake, synthesis and oxidation were increased in the diabetic hearts, and these increases were all reduced by liraglutide. In addition, liraglutide increased expression of Sirt1 and phosphorylated AMPK in the diabetic hearts. Conclusions: Liraglutide may have a beneficial effect on cardiac steatosis, DAG-PKC-NAD(P)H pathway, oxidative stress and apoptosis via activation of AMPK-Sirt1 pathway, independently of a glucose-lowering effect.

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