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Open Access Uncoupling protein 2 facilitates insulin-elicited protection against lipopolysaccharide-induced myocardial dysfunction

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Sepsis-induced myocardial dysfunction is a critical cause of high mortality among patients with sepsis. Previously, insulin has been suggested to protect against lethal endotoxemia, while uncoupling protein 2 (UCP2) has been reported to exert beneficial effects against sepsis. Thus, this study aimed to investigate whether UCP2 is involved in insulin-elicited protection against myocardial dysfunction in lipopolysaccharide (LPS)-induced sepsis. Treatment of male SD rats with insulin for 30 min before LPS challenge improved the survival and cardiac function in endotoxemic rats, which was likely due to an insulin-dependent reduction of serum lactate dehydrogenase (LDH) activity and cardiac troponin T (cTn-T) levels, mitochondrial oxidative stress, and cardiomyocyte apoptosis. Insulin treatment also increased the Bcl-2/Bax ratio, prevented the release of cytochrome c into the cytosol, and reduced cleaved caspase-9 levels, which was determined by purifying the proteins using the His-tag Magnetic Bead Purification Kit (Fe3O4). Moreover, UCP2 was found to be upregulated in endotoxemic rats which were pretreated with insulin. To determine whether the apoptotic role of insulin is associated with UCP2 upregulation, we examined the effects of genipin, a UCP2 inhibitor, on insulin activity in LPS-treated H9c2 cells. Insulin strongly attenuated LPS-induced H9c2 cell apoptosis and stimulated UCP2 expression. However, genipin treatment eliminated the antiapoptotic effects of insulin. Thus, our results demonstrate that insulin-induced UCP2 upregulation plays a role in the protective effect of insulin against LPS-induced myocardial dysfunction.
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Keywords: Apoptosis; Cardiomyocyte; Endotoxemia; Fe3O4; Mitochondria; Oxidative Stress; Uncoupling Protein 2

Document Type: Research Article

Affiliations: 1: Department of Pediatrics, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, PR China 2: Department of Pediatrics, Central Hospital of Panyu District, Guangzhou 511400, Guangdong, PR China 3: Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, PR China 4: Department of Anesthesiology, Zhuhai People’s Hospital, Jinan University, Zhuhai 519000, Guangdong, PR China

Publication date: March 1, 2020

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  • Materials Express is a peer-reviewed multidisciplinary journal reporting emerging researches on materials science, engineering, technology and biology. Cutting-edge researches on the synthesis, characterization, properties, and applications of a very wide range of materials are covered for broad readership; from physical sciences to life sciences. In particular, the journal aims to report advanced materials with interesting electronic, magnetic, optical, mechanical and catalytic properties for industrial applications.
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