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Hyperglycemia and cardiomyocytes

Yao-Te Huang, Chung-Hung Liu, Yao-Chih Yang, Ritu Aneja, Su-Ying Wen, Chih-Yang Huang, Wei-Wen Kuo
The prevalence of chronic hyperglycemia and its complications, imposing a critical burden on the worldwide economy and the global healthcare system, is a pressing issue. Mounting evidence indicates that oxidative stress and hypoxia, two noticeable features of hyperglycemia, play a joint crucial role in mediating cellular apoptosis. However, the underlying detailed molecular mechanism remains elusive. Triggered by the observation that insulin-like growth factor (IGF1)-binding protein 3 (IGFBP3) can mediate, in renal cells, high-glucose-induced apoptosis by elevating oxidative stress, we wish to, in this study, know whether or not the similar scenario holds in cardiac cells and, if so, to find its relevant molecular key players, thereby dissecting the underlying molecular pathway...
January 19, 2019: Journal of Cellular Physiology
Shengnan Wu, Qiulun Lu, Ye Ding, Yin Wu, Yu Qiu, Pei Wang, Xiaoxiang Mao, Kai Huang, Zhonglin Xie, Ming-Hui Zou
BACKGROUND: FUN14 domain containing 1 (Fundc1), an outer mitochondrial membrane protein, is important for mitophagy and mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs). The roles of Fundc1 and MAMs in diabetic hearts remain unknown. The aims of this study therefore, were to determine if the diabetes-induced Fundc1 expression could increase MAM formation, and whether disruption of MAM formation improves diabetic cardiac function. METHODS: Levels of FUNDC1 were examined in the hearts from diabetic patients and nondiabetic donors...
January 16, 2019: Circulation
Zhen-Guo Ma, Chun-Yan Kong, Peng Song, Xin Zhang, Yu-Pei Yuan, Qi-Zhu Tang
Our previous study found that geniposide, an agonist of glucagon-like peptide-1 receptor (GLP-1R), protected against cardiac hypertrophy via the activation of AMP-activated protein kinase α (AMPK α ). However, the effects of geniposide on obesity-related cardiac injury remain unknown. Here, we examine whether geniposide attenuates obesity-related cardiac dysfunction. Adult mice were fed a high-fat diet (HFD) for 24 weeks to induce obesity, with the last 3 weeks including a 21-day treatment with geniposide...
2018: Oxidative Medicine and Cellular Longevity
Ravichandra Shivalingappa Davargaon, Asha Devi Sambe, Subramanyam Muthangi V V
Oxidative stress (OS) has been implicated in a variety of pathological conditions, including diabetes mellitus, characterized by hyperglycemia. In the present study, OS induced by hyperglycemia and the effect of trolox, a vitamin E analog, were studied in cardiomyocytes and H9c2 cells exposed to 15 to 33 mM glucose (HG) for 24 to 72 hours in Dulbecco modified Eagle medium. Cells treated wirh 24 or 33 mM glucose for 24 hours or above showed decreased viability and adenosine triphosphate (ATP) content with a concomitant increase in radicals of oxygen species, calcium (Ca2+ ), mitochondrial permeability transition, and oxidative markers, confirming that the cells were under stress...
December 4, 2018: Journal of Biochemical and Molecular Toxicology
Aysegul Durak, Yusuf Olgar, Sinan Degirmenci, Erman Akkus, Erkan Tuncay, Belma Turan
BACKGROUND: Metabolic syndrome (MetS) is a prevalent risk factor for cardiac dysfunction. Although SGLT2-inhibitors have important cardioprotective effects in hyperglycemia, their underlying mechanisms are complex and not completely understood. Therefore, we examined mechanisms of a SGLT2-inhibitor dapagliflozin (DAPA)-related cardioprotection in overweight insulin-resistant MetS-rats comparison with insulin (INSU), behind its glucose-lowering effect. METHODS: A 28-week high-carbohydrate diet-induced MetS-rats received DAPA (5 mg/kg), INSU (0...
November 17, 2018: Cardiovascular Diabetology
Yusuf Olgar, Belma Turan
Sodium-glucose cotransporter 2 (SGLT2) inhibitors showed significant effects in patients with diabetes or metabolic syndrome (MetS) with high cardiovascular risk. Although the increased intracellular Zn2+ level ([Zn2+ ]i ), oxidative stress, and altered cardiac matrix metalloproteinases (MMPs) in diabetic cardiomyopathy can intersect with different signaling pathways, the exact mechanisms are not known yet. Since either MMPs or SGLT2 have important roles in cardiac-fibrosis under hyperglycemia, we aimed to examine the role of SGLT2 inhibitor dapagliflozin (DAP) on cardiac Zn2+ -transporters responsible for [Zn2+ ]i -regulation, comparison to insulin (INS), together with MMP levels and systemic oxidative stress status in MetS-rats...
November 16, 2018: Canadian Journal of Physiology and Pharmacology
Jakob G Knudsen, Alexander Hamilton, Reshma Ramracheya, Andrei I Tarasov, Melissa Brereton, Elizabeth Haythorne, Margarita V Chibalina, Peter Spégel, Hindrik Mulder, Quan Zhang, Frances M Ashcroft, Julie Adam, Patrik Rorsman
Diabetes is a bihormonal disorder resulting from combined insulin and glucagon secretion defects. Mice lacking fumarase (Fh1) in their β cells (Fh1βKO mice) develop progressive hyperglycemia and dysregulated glucagon secretion similar to that seen in diabetic patients (too much at high glucose and too little at low glucose). The glucagon secretion defects are corrected by low concentrations of tolbutamide and prevented by the sodium-glucose transport (SGLT) inhibitor phlorizin. These data link hyperglycemia, intracellular Na+ accumulation, and acidification to impaired mitochondrial metabolism, reduced ATP production, and dysregulated glucagon secretion...
November 1, 2018: Cell Metabolism
Jing Tian, Wenzhu Tang, Ming Xu, Chen Zhang, Pei Zhao, Tongtong Cao, Xiaoli Shan, Rong Lu, Wei Guo
BACKGROUND/AIMS: Shengmai San (SMS), prepared from Panax ginseng, Ophiopogon japonicus, and Schisandra chinensisin, has been widely used to treat ischemic disease. In this study, we investigated whether SMS may exert a beneficial effect in diabetic cardiomyopathy through improvement of mitochondrial lipid metabolism. METHODS: A leptin receptor-deficient db/db mouse model was utilized, and lean age-matched C57BLKS mice served as non-diabetic controls. Glucose and lipid profiles, myocardial structure, dimension, and function, and heart weight to tibial length ratio were determined...
2018: Cellular Physiology and Biochemistry
Gwo-Jyh Chang, Yung-Hsin Yeh, Wei-Jan Chen, Yu-Shien Ko, Jong-Hwei S Pang, Hsiao-Yu Lee
Diabetic patients with cardiomyopathy show a higher incidence of arrhythmias and sudden death. Chronic hyperglycemia induces the formation of advanced glycation end products (AGEs), which contribute to the pathogenesis of diabetic cardiomyopathy. This study investigated whether inhibition of AGEs formation by aminoguanidine (AG) could prevent the cardiac electromechanical and arrhythmogenic remodeling in diabetes mellitus. Streptozotocin-induced diabetic rats received AG (100 mg/kg daily, IP) or vehicle (normal saline, IP) for 5 weeks...
October 31, 2018: Journal of Pharmacology and Experimental Therapeutics
Weijian Hang, Benhong He, Jiehui Chen, Liangtao Xia, Bing Wen, Tao Liang, Xu Wang, Qianying Zhang, Yue Wu, Qingjie Chen, Juan Chen
Background: Type II diabetes (T2D)-induced cardiomyocyte hypertrophy is closely linked to the impairment of mitochondrial function. Berberine has been shown to be a promising effect for hypoglycemia in T2D models. High glucose-induced cardiomyocyte hypertrophy in vitro has been reported. The present study investigated the protective effect and the underlying mechanism of berberine on high glucose-induced H9C2 cell line. Methods: High glucose-induced H9C2 cell line was used to mimic the hyperglycemia resulting in cardiomyocyte hypertrophy...
2018: Frontiers in Pharmacology
Chen Zhao, Qile Shen
Hyperglycemia may induce diabetic cardiomyopathy (DC). In the current study, the mechanism underlying the alleviation of high glucose (HG)‑induced impairments in the proliferation of H9c2 embryo cardiomyocyte proliferation by small ubiquitin‑like modifier 2 (SUMO2) overexpression was investigated. H9c2 cell morphology was identified as classical long shuttle type by optical microscopy. The viability of HG‑injured H9c2 cells was evaluated by a Cell Counting Kit‑8 assay and the results indicated that viability was inhibited in a dose‑dependent (5...
December 2018: Molecular Medicine Reports
Yan-Jun Song, Chong-Bin Zhong, Xian-Bao Wang
Acute myocardial infarction is a major cause of death worldwide. The most important therapy for limiting ischemic injury and infarct size is timely and efficient myocardial reperfusion treatment, which may instead induce cardiomyocyte necrosis due to myocardial ischemia-reperfusion (I/R) injury. Heat shock protein 70 (HSP70), a stress-inducible protein, is overexpressed during myocardial I/R. The induced HSP70 is shown to regulate several intracellular proteins (e.g., transcription factors, enzymes, and apoptosis-related proteins) and signaling pathways (e...
August 21, 2018: Journal of Cellular Physiology
Belma Turan
Zinc (mostly as free/labile Zn2+ ) is an essential structural constituent of many proteins, including enzymes in cellular signaling pathways via functioning as an important signaling molecule in mammalian cells. In cardiomyocytes at resting condition, intracellular labile Zn2+ concentration ([Zn2+ ]i ) is in the nanomolar range, whereas it can increase dramatically under pathological conditions, including hyperglycemia, but the mechanisms that affect its subcellular redistribution is not clear. Therefore, overall, very little is known about the precise mechanisms controlling the intracellular distribution of labile Zn2+ , particularly via Zn2+ transporters during cardiac function under both physiological and pathophysiological conditions...
August 8, 2018: Biological Trace Element Research
Kunal Sikder, Sanket Kumar Shukla, Neel Patel, Harpreet Singh, Khadija Rafiq
BACKGROUND/AIMS: Systemic hyperlipidemia and intracellular lipid accumulation induced by chronic high fat diet (HFD) leads to enhanced fatty acid oxidation (FAO) and ketogenesis. The present study was aimed to determine whether activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) by surplus free fatty acids (FA) in hyperlipidemic condition, has a positive feedback regulation over FAO and ketogenic enzymes controlling lipotoxicity and cardiac apoptosis. METHODS: 8 weeks old C57BL/6 wild type (WT) or PPAR-γ-/- mice were challenged with 16 weeks 60% HFD to induce obesity mediated type 2 diabetes mellitus (T2DM) and diabetic cardiomyopathy...
2018: Cellular Physiology and Biochemistry
Linda Alex, Ilaria Russo, Volodymir Holoborodko, Nikolaos G Frangogiannis
Heart failure with preserved ejection fraction (HFpEF) is caused, or exacerbated by, a wide range of extracardiac conditions. Diabetes, obesity, and metabolic dysfunction are associated with a unique HFpEF phenotype, characterized by inflammation, cardiac fibrosis, and microvascular dysfunction. Development of new therapies for HFpEF is hampered by the absence of reliable animal models. The leptin-resistant db/ db mouse has been extensively studied as a model of diabetes-associated cardiomyopathy; however, data on the functional and morphological alterations in db/ db hearts are conflicting...
October 1, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Woong Bi Jang, Ji Hye Park, Seung Taek Ji, Na Kyung Lee, Da Yeon Kim, Yeon Ju Kim, Seok Yun Jung, Songhwa Kang, Shreekrishna Lamichane, Babita Dahal Lamichane, Jongseong Ha, Jisoo Yun, Hyung Ryong Moon, Sang Hong Baek, Hae Young Chung, Sang-Mo Kwon
Diabetic cardiomyopathy (DCM) is tightly linked to heart disorders and dysfunction or death of the cardiomyocytes including resident cardiac progenitor cells (CPCs) in diabetic patients. In order to restore loss of function of resident or transplanted CPCs, much research has focused on novel therapeutic strategies including the discovery of novel function-modulating factors such as reactive oxygen species (ROS) scavengers. Here, we developed and defined a novel antioxidant, MHY-1684, for enhancing the angiogenic potential of CPCs against ROS-related DCM...
2018: Oxidative Medicine and Cellular Longevity
Lorna J Daniels, Rachel S Wallace, Olivia M Nicholson, Genevieve A Wilson, Fiona J McDonald, Peter P Jones, J Chris Baldi, Regis R Lamberts, Jeffrey R Erickson
BACKGROUND: Calcium/calmodulin-dependent kinase II-delta (CaMKIIδ) activity is enhanced during hyperglycemia and has been shown to alter intracellular calcium handling in cardiomyocytes, ultimately leading to reduced cardiac performance. However, the effects of CaMKIIδ on cardiac contractility during type 2 diabetes are undefined. METHODS: We examined the expression and activation of CaMKIIδ in right atrial appendages from non-diabetic and type 2 diabetic patients (n = 7 patients per group) with preserved ejection fraction, and also in right ventricular tissue from Zucker Diabetic Fatty rats (ZDF) (n = 5-10 animals per group) during early diabetic cardiac dysfunction, using immunoblot...
June 14, 2018: Cardiovascular Diabetology
Miao Guo, Hong-Xia Wang, Wen-Jun Chen
Diabetic cardiomyopathy is a cascade of complex events leading to eventual heart failure in diabetes. JQ1, one of Bromodomain and extra-terminal domain (BET) protein inhibitors, has exerted therapeutic effects on cancer proliferation, inflammation and cardiovascular disease. Recently, JQ1 was reported to protect mice from bleomycin-induced lung fibrosis and reverse the fibrotic response in carbon tetrachloride-induced liver fibrosis. However, its role in diabetic cardiomyopathy remains to be clarified. Our results indicated that JQ1 treatment suppressed cardiac fibrosis and improved cardiac function in a STZ-induced diabetic mouse model...
August 1, 2018: Toxicology and Applied Pharmacology
Nur Liyana Mohammed Yusof, Satirah Zainalabidin, Norsyahida Mohd Fauzi, Siti Balkis Budin
Diabetes mellitus is often associated with cardiac functional and structural alteration, an initial event leading to cardiovascular complications. Roselle (Hibiscus sabdariffa) has been widely proven as an antioxidant and recently has incited research interest for its potential in treating cardiovascular disease. Therefore, this study aimed to determine the cardioprotective effects of H. sabdariffa (roselle) polyphenol-rich extract (HPE) in type-1-induced diabetic rats. Twenty-four male Sprague-Dawley rats were randomized into 4 groups (n = 6/group): nondiabetic, diabetic alone (DM), diabetic supplemented with HPE (DM+HPE), and diabetic supplemented with metformin...
May 4, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Jun Hou, Dezhi Zheng, Wenjing Xiao, Dandan Li, Jie Ma, Yonghe Hu
Mangiferin functions as a perfect anti-oxidative compound in the diabetic heart, however, the exact mechanism remains to be elucidated. Here, we show the cardioprotective effect of mangiferin under high glucose-induced cardiotoxic condition mainly contributed to enhanced autophagy via suppressing mTORC1 downstream signal transduction. Primary neonatal rat cardiomyocytes were cultured to detect myocytes injury, autophagy, and related signal transduction under different doses of glucose and mangiferin treatment...
2018: Frontiers in Pharmacology
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