Changes of myocardial function in diabetic rats and its mechanism

doi:10.12047/j.cjap.5808.2019.083

Abstract

Abstract: Objective: To investigate the role of calcium-sensing receptor (CaSR) in the decrease of cardiac function in type 2 diabetic rats. Methods: Wistar rats were randomly divided into 3 groups including control, diabetic-4 week and diabetic-8 week groups. Rats in the diabetes group were fed with high-glucose and high-fat diet, and intraperitoneal injection of streptozocin (STZ,30 mg/kg) was conducted 4 weeks later to establish a type 2 diabetes model. Cardiac morphological changes were observed by HE staining, cardiac function was detected by echocardiography, and CaSR and PKC-αprotein expressions in cardiac tissue were detected by Western blot. Results: Compared with the control group, the myocardium of diabetic rats showed irregular contraction zone, decreased expression of CaSR protein, increased expression of PKC-α protein, decreased systolic and diastolic functions, and gradually worsened with the prolongation of the course of the disease. Conclusion: Hyperglycemia inhibits the expression of CaSR protein in myocardium of diabetic rats by activating PKC-α, which can cause intracellular calcium disorder and lead to decreased cardiac function.

Key words: calcium-sensing receptor, type 2 diabetes, cardiac function

BAI Shu-zhi, XU Na, WANG Yue-hong, LI Hong-zhu, LI Hong-xia. Changes of myocardial function in diabetic rats and its mechanism[J]. CJAP, 2019, 35(5): 390-392.

References

[1] Blaslov K, Naranda FS, Kruljac I, et al. Treatment approach to type 2 diabetes: Past, present and future[J]. World J Diabetes, 2018, 9(12): 209-219.
[2] Maffei A, Lembo G, Carnevale D. PI3Kinases in diabetes mellitus and its related complications[J]. Int J Mol Sci, 2018, 19(12): E4098-E4113.
[3] Wang R, Xu C, Zhao W, et al. Calcium and polyamine regulated calcium-sensing receptors in cardiac tissues[J]. Eur J Biochem, 2003, 270(12): 2680-2688.
[4] Wang J, Li Z, Wang Y, et al. Qiliqiangxin enhances cardiac glucose metabolism and improves diastolic function in spontaneously hypertensive rats[J]. Evid Based Complement Alternat Med, 2017, 2017: 3197320-3197330.
[5] 杨锐, 贾强, 刘小粉, 等. 硫化氢对大鼠糖尿病心肌病氧化应激及内质网应激的影响[J]. 中国应用生理学杂志, 2016, 32(1): 8-12.
[6] Wang-Soo Lee, Jaetaek Kim. Diabetic cardiomyopathy: where we are and where we are going[J]. Korean J Intern Med, 2017, 32(3): 404-421.
[7] 杨帆, 韩钰, 丛恬駪, 等. 薯蓣皂苷对大鼠心肌收缩与钠-钙交换体的影响[J]. 中国应用生理学杂志, 2016, 32(3): 209-213.
[8] Riehle C, Bauersachs J. Of mice and men: models and mechanisms of diabetic cardiomyopathy[J]. Basic Res Cardiol, 2019, 114(1): 2-23.
[9] Gorvin CM, Hannan FM, Cranston T, et al. Cinacalcet rectifies hypercalcemia in a patient with familial hypocalciuric hypercalcemia type 2 (FHH2) caused by a germline loss-of-function Gα11 mutation[J]. J Bone Miner Res, 2018, 33(1): 32-41.
[10]Sims MW, Winter J, Brennan S, et al. PKC-mediated toxicity of elevated glucose concentration on cardiomyocyte function[J].Am J Physiol Heart Circ Physiol, 2014, 07(4): H587-H597.
[11]Sharp TE 3rd, Kubo H, Berretta RM, et al. Protein kinase C inhibition with ruboxistaurin increases contractility and reduces heart size in a swine model of Hheart failure with reduced ejection fraction[J]. JACC Basic Transl Sci, 2017, 2(6): 669-683.
[12]Lei CT, Wei YH, Tang H, et al. PKC-α triggers EGFR ubiquitination, endocytosis and ERK activation in podocytes stimulated with high glucose[J]. Cell Physiol Biochem, 2017, 42(1): 281-294.

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