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GLP-1 analog liraglutide protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats.
Atherosclerosis. 2015 May; 240(1):250-9.A

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 (0.3 mg/kg/12 h) 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.

Authors+Show Affiliations

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: toyoshi@intmed3.med.kyushu-u.ac.jp.Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25818251

Citation

Inoue, Tomoaki, et al. "GLP-1 Analog Liraglutide Protects Against Cardiac Steatosis, Oxidative Stress and Apoptosis in Streptozotocin-induced Diabetic Rats." Atherosclerosis, vol. 240, no. 1, 2015, pp. 250-9.
Inoue T, Inoguchi T, Sonoda N, et al. GLP-1 analog liraglutide protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats. Atherosclerosis. 2015;240(1):250-9.
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, 240(1), 250-9. https://doi.org/10.1016/j.atherosclerosis.2015.03.026
Inoue T, et al. GLP-1 Analog Liraglutide Protects Against Cardiac Steatosis, Oxidative Stress and Apoptosis in Streptozotocin-induced Diabetic Rats. Atherosclerosis. 2015;240(1):250-9. PubMed PMID: 25818251.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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, Y1 - 2015/03/18/ PY - 2014/09/03/received PY - 2015/03/16/revised PY - 2015/03/17/accepted PY - 2015/3/31/entrez PY - 2015/3/31/pubmed PY - 2016/1/5/medline KW - Cardiac steatosis KW - Diabetic cardiomyopathy KW - Glucagon-like peptide-1 KW - Oxidative stress KW - Protein kinase C SP - 250 EP - 9 JF - Atherosclerosis JO - Atherosclerosis VL - 240 IS - 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 (0.3 mg/kg/12 h) 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. SN - 1879-1484 UR - https://www.unboundmedicine.com/medline/citation/25818251/GLP_1_analog_liraglutide_protects_against_cardiac_steatosis_oxidative_stress_and_apoptosis_in_streptozotocin_induced_diabetic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(15)00186-0 DB - PRIME DP - Unbound Medicine ER -