Changjiang Ying1, Ting Liu2, Hongwei Ling1, Mingyue Cheng3, Xiaoyan Zhou4, Shanshan Wang2, Yizhen Mao2, Lei Chen2, Runze Zhang5, Wei Li1. 1. 1 Department of Endocrinology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. 2. 2 The Graduate School, Xuzhou Medical University, Xuzhou, China. 3. 3 Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. 4. 4 Laboratory of Morphology, Xuzhou Medical University, Xuzhou, China. 5. 5 Xuzhou Medical University, Xuzhou, China.
Abstract
OBJECTIVE: To study the effect of blood glucose variability on cardiac fibrosis and its mechanism in a model of diabetic cardiomyopathy. METHODS: A total of 45 Sprague Dawley rats were randomly divided into three groups: control, control diabetes mellitus and fluctuated blood glucose groups. Fluctuated blood glucose was induced by daily subcutaneous insulin and intraperitoneal glucose injections at different time points. Blood lipids and glycosylated haemoglobin A1c were assessed. Super oxide dismutase activity and malondialdehyde level in rat heart homogenates were determined by assay kit. Structural cardiac tissue changes were observed by haematoxylin and eosin staining and Masson's trichrome staining. Collagen type 3, fibronectin, phosphorylated Ser/Thr protein kinase, phosphorylated glycogen synthase kinase-3 beta, glycogen synthase kinase-3 beta, nuclear factor kappa-light-chain-enhancer of activated B cells, cleaved-cysteinyl aspartate-specific proteinase-3 (caspase-3) and tumour necrosis factor-α levels were determined by western blot. RESULTS: Compared with the control group, cardiac fibrosis and oxidative stress in heart tissue were aggravated in diabetic rats, which were more pronounced in glucose variability rats. However, the expression levels of AKT and glycogen synthase kinase-3 beta were not significantly different in three groups, but the expression levels of phosphorylated Ser/Thr protein kinase and phosphorylated glycogen synthase kinase-3 beta were significantly decreased in the control diabetes mellitus and fluctuated blood glucose groups compared to control group, and levels in the fluctuated blood glucose group were significantly less than in the control diabetes mellitus group. In addition, the expression levels of nuclear factor kappa B and caspase-3 in both the control diabetes mellitus and fluctuated blood glucose groups were higher than in the control group, with the highest levels measured in the fluctuated blood glucose group. CONCLUSION: Blood glucose variability can aggravate heart tissue fibrosis, possibly involving oxidative stress by inhibiting AKT signalling path.
OBJECTIVE: To study the effect of blood glucose variability on cardiac fibrosis and its mechanism in a model of diabetic cardiomyopathy. METHODS: A total of 45 Sprague Dawley rats were randomly divided into three groups: control, control diabetes mellitus and fluctuated blood glucose groups. Fluctuated blood glucose was induced by daily subcutaneous insulin and intraperitoneal glucose injections at different time points. Blood lipids and glycosylated haemoglobin A1c were assessed. Super oxide dismutase activity and malondialdehyde level in rat heart homogenates were determined by assay kit. Structural cardiac tissue changes were observed by haematoxylin and eosin staining and Masson's trichrome staining. Collagen type 3, fibronectin, phosphorylated Ser/Thr protein kinase, phosphorylated glycogen synthase kinase-3 beta, glycogen synthase kinase-3 beta, nuclear factor kappa-light-chain-enhancer of activated B cells, cleaved-cysteinyl aspartate-specific proteinase-3 (caspase-3) and tumour necrosis factor-α levels were determined by western blot. RESULTS: Compared with the control group, cardiac fibrosis and oxidative stress in heart tissue were aggravated in diabeticrats, which were more pronounced in glucose variability rats. However, the expression levels of AKT and glycogen synthase kinase-3 beta were not significantly different in three groups, but the expression levels of phosphorylated Ser/Thr protein kinase and phosphorylated glycogen synthase kinase-3 beta were significantly decreased in the control diabetes mellitus and fluctuated blood glucose groups compared to control group, and levels in the fluctuated blood glucose group were significantly less than in the control diabetes mellitus group. In addition, the expression levels of nuclear factor kappa B and caspase-3 in both the control diabetes mellitus and fluctuated blood glucose groups were higher than in the control group, with the highest levels measured in the fluctuated blood glucose group. CONCLUSION:Blood glucose variability can aggravate heart tissue fibrosis, possibly involving oxidative stress by inhibiting AKT signalling path.