Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes

Wu, Mingyang; Yang, Yizhou; Wang, Meng; Zeng, Fangfang; Qin, Li; Liu, Wenjuan; Guo, Shizhe; He, Min; Wang, Yi; Huang, Jie; Zhou, Lei; Li, Yiming; Hu, Ji; Gong, Wei; Zhang, Zhaoyun

doi:10.3389/fphar.2018.00855

Cited by 6 publications

(3 citation statements)

References 58 publications

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“…Increased serum TNF-α and IL-6 levels of diabetic patients are associated with LV diastolic dysfunction [ 54 ]. In our experiment, elevation of Il1b , Il6 , Tnf and Ccl2 in the left ventricle indicate the activation of inflammatory signaling pathways, similarly to other T1DM models [ 55 , 56 ]. We showed that DM-induced cardiac inflammation is diminished by DAPA treatment.…”

Section: Discussionsupporting

confidence: 74%

SGLT2 inhibitor dapagliflozin prevents atherosclerotic and cardiac complications in experimental type 1 diabetes

et al. 2022

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Introduction Cardiovascular disease (CVD) is two to five times more prevalent in diabetic patients and is the leading cause of death. Therefore, identification of novel therapeutic strategies that reduce the risk of CVD is a research priority. Clinical trials showed that reduction in the relative risk of heart failure by sodium-glucose cotransporter 2 inhibitors (SGLT2i) are partly beyond their glucose lowering effects, however, the molecular mechanisms are still elusive. Here we investigated the role of SGLT2i dapagliflozin (DAPA) in the prevention of diabetes-induced cardiovascular complications. Methods Type 1 diabetes was induced with streptozotocin (65 mg/bwkg, ip.) in adult, male Wistar rats. Following the onset of diabetes rats were treated for six weeks with DAPA (1 mg/bwkg/day, po.). Results DAPA decreased blood glucose levels (D: 37±2.7 vs. D+DAPA: 18±5.6 mmol/L; p<0.05) and prevented metabolic decline. Aortic intima-media thickening was mitigated by DAPA. DAPA abolished cardiac hypertrophy, and myocardial damage. Cardiac inflammation and fibrosis were also moderated after DAPA treatment. Conclusions These data support the preventive and protective role of SGLT2i in diabetes-associated cardiovascular disease. SGLT2i may provide novel therapeutic strategy to hinder the development of cardiovascular diseases in type 1 diabetes, thereby improve the outcomes.

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Section: Discussionsupporting

confidence: 74%

SGLT2 inhibitor dapagliflozin prevents atherosclerotic and cardiac complications in experimental type 1 diabetes

et al. 2022

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“…On the other hand, hypoperfusion of the liver and pancreas, treatment with β -blockers and diuretics, and dysfunction of the autonomic nervous system due to heart failure can impair glucose metabolism ( Ansari et al, 2019b ). During anti-diabetic drug discovery, targeting common molecules between diabetes mellitus and cardiovascular diseases [such as peroxisome proliferator-activated receptors (PPARs), which are involved in insulin resistance, glucose and lipid metabolism, and systolic or diastolic activity of the left ventricle] may provide a solution to these reciprocal complications ( Wu et al, 2018 ). Preclinical studies have demonstrated that PPAR activation can upregulate fatty acid oxidation genes, improve ventricular contraction, and reduce cardiac remodeling via anti-inflammatory, anti-oxidant, anti-fibrotic, and anti-apoptotic mechanisms ( Kanwal et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion

et al. 2021

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Matrine, an active component of Sophora flavescens Ait root extracts, has been used in China for years to treat cancer and viral hepatitis. In the present study, we explored the effects of matrine on hyperglycemia-treated cardiomyocytes. Cardiomyocyte function, oxidative stress, cellular viability, and mitochondrial fusion were assessed through immunofluorescence, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assays, and RNA interference. Matrine treatment suppressed hyperglycemia-induced oxidative stress in cardiomyocytes by upregulating transcription of nuclear factor erythroid 2-like 2 and heme oxygenase-1. Matrine also improved cardiomyocyte contractile and relaxation function during hyperglycemia, and it reduced hyperglycemia-induced cardiomyocyte death by inhibiting mitochondrial apoptosis. Matrine treatment increased the transcription of mitochondrial fusion-related genes and thus attenuated the proportion of fragmented mitochondria in cardiomyocytes. Inhibiting mitochondrial fusion by knocking down mitofusin 2 (Mfn2) abolished the cardioprotective effects of matrine during hyperglycemia. These results demonstrate that matrine could be an effective drug to alleviate hyperglycemia-induced cardiomyocyte damage by activating Mfn2-induced mitochondrial fusion.

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“…In this study, we used streptozocin to induce diabetes in rats as previously described (25-28). The inflammatory process and potocyte injury in the rats with DN were subsequently analyzed.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Sirt6 promotes M2�macrophage transformation, alleviating renal injury in diabetic nephropathy

Chen

Wang³

et al. 2019

Int J Oncol

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In this study, we aimed to investigate the associations between Sirt6, macrophages and diabetic nephropathy (DN). Immunohistochemical, western blot and RT-qPCR analyses were performed to detect the expression levels of Sirt6, the markers of podocytes and monocytes and related inflammatory factors in the tissues of rats with streptozocin-induced DN. A series of cell experiments in isolated culture or the co-culture of macrophages and podocytes were conducted to examine the effects of the overexpression of Sirt6 on macrophage transformation, podocyte apoptosis and associated genes, and analyses were performed using RT-qPCR, flow cytometry and western blot analysis, where appropriate. In the rat model of DN, injured podocytes were represented by the decreased protein expression levels of Nephrin and Sirt6, and by an increased Desmin expression. Additionally, the M1 phenotype transformation of macrophages was evidenced by the increased expression levels of CD86, tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS), and by the decreased expression levels of CD206, Sirt6, interleukin (IL)-4 and IL-10. In vitro assays of macrophages and podocytes demonstrated that glucose promoted macrophage M1 transformation and podocyte apoptosis in a dose-dependent manner and attenuated Sirt6 expression. Macrophages transformed into the M2 phenotype following the overexpression of Sirt6 by the successful transfection of macrophages with a Sirt6 overexpression plasmid. Sirt6 was also overexpressed in podocytes. In a Transwell co-culture system, the overexpression of Sirt6 in macrophages (but not the overexpression of Sirt6 in podocytes) protected the podocytes from high-glucose-induced injury. However, the apoptosis of the podocytes overexpressing Sirt6 (induced by transfection with a Sirt6 overexpression plasmid) still increased when these podocytes were co-cultured with macrophages in high-glucose medium. These protective effects were evidenced by the inhibition of apoptosis, the upregulation of the expression levels of Bcl-2 and CD206, as well as by the decreased expression levels of Bax and CD86. On the whole, the findings of this study suggest that Sirt6 protects podocytes against injury in a mimicked diabetic kidney microenvironment by activating M2 macrophages, indicating that Sirt6 can act as an immune response regulatory factor in DN-associated renal inflammatory injury.

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Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes

Cited by 6 publications

References 58 publications

SGLT2 inhibitor dapagliflozin prevents atherosclerotic and cardiac complications in experimental type 1 diabetes

SGLT2 inhibitor dapagliflozin prevents atherosclerotic and cardiac complications in experimental type 1 diabetes

RETRACTED: Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion

Overexpression of Sirt6 promotes M2�macrophage transformation, alleviating renal injury in diabetic nephropathy

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