Gaber E M, Jayaprakash P, Qureshi M A, Parekh K, Oz M, Adrian T E, Howarth F C
Department of Physiology, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Department of Pharmacology, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Exp Physiol. 2014 Jun;99(6):881-93. doi: 10.1113/expphysiol.2013.077594. Epub 2014 Mar 28.
There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM), and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients. A variety of diastolic and systolic dysfunctions have been demonstrated in type 2 diabetic heart. The consumption of sugar-sweetened beverages has been linked to rising rates of obesity, which in turn is a risk factor for development of T2DM. In this study, the effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca(2+) transport in the Goto-Kakizaki T2DM rat heart were investigated. Genes encoding cardiac muscle proteins (Myh7, Mybpc3, Myl1, Myl3 and Mylpf), intercellular proteins (Gja4), cell membrane transport (Atp1b1), calcium channels (Cacna1c, Cacna1g and Cacnb1) and potassium channels (Kcnj11) were upregulated and genes encoding potassium channels (Kcnb1) were downregulated in GK compared with control rats. Genes encoding cardiac muscle proteins (Myh6, Mybpc3 and Tnn2), intercellular proteins (Gja1 and Gja4), intracellular Ca(2+) transport (Atp2a1 and Ryr2), cell membrane transport (Atp1a2 and Atp1b1) and potassium channel proteins (Kcnj2 and Kcnj8) were upregulated and genes encoding cardiac muscle proteins (Myh7) were downregulated in control rats fed sucrose compared with control rats. Genes encoding cardiac muscle proteins (Myh7) and potassium channel proteins (Kcnj11) were downregulated in control and GK rats fed sucrose compared with control and GK rats, respectively. The amplitude of shortening was reduced in myocytes from the control-sucrose group compared with control rats and in the GK-sucrose group compared with GK rats. The amplitude of the Ca(2+) transient was increased in myocytes from control-sucrose compared with control rats and decreased in GK-sucrose compared with GK rats. Subtle alterations in the pattern of expression of genes encoding a variety of cardiac muscle proteins are associated with changes in shortening and intracellular Ca(2+) transport in ventricular myocytes from GK T2DM and control rats fed a sucrose-enriched diet.
2型糖尿病（T2DM）在全球的患病率急剧上升，心血管疾病是糖尿病患者发病和死亡的主要原因。2型糖尿病心脏已出现各种舒张和收缩功能障碍。含糖饮料的消费与肥胖率上升有关，而肥胖又是T2DM发病的一个危险因素。在本研究中，研究了富含蔗糖的饮食对Goto-Kakizaki T2DM大鼠心脏基因表达模式、收缩和Ca(2+)转运的影响。与对照大鼠相比，GK大鼠中编码心肌蛋白（Myh7、Mybpc3、Myl1、Myl3和Mylpf）、细胞间蛋白（Gja4）、细胞膜转运蛋白（Atp1b1）、钙通道（Cacna1c、Cacna1g和Cacnb1）和钾通道（Kcnj11）的基因上调，而编码钾通道（Kcnb1）的基因下调。与对照大鼠相比，喂食蔗糖的对照大鼠中编码心肌蛋白（Myh6、Mybpc3和Tnn2）、细胞间蛋白（Gja1和Gja4）、细胞内Ca(2+)转运蛋白（Atp2a1和Ryr2）、细胞膜转运蛋白（Atp1a2和Atp1b1）和钾通道蛋白（Kcnj2和Kcnj8）的基因上调，而编码心肌蛋白（Myh7）的基因下调。与对照和GK大鼠相比，喂食蔗糖的对照和GK大鼠中编码心肌蛋白（Myh7）和钾通道蛋白（Kcnj11）的基因分别下调。与对照大鼠相比，对照-蔗糖组心肌细胞的缩短幅度降低，与GK大鼠相比，GK-蔗糖组心肌细胞的缩短幅度也降低。与对照大鼠相比，对照-蔗糖组心肌细胞Ca(2+)瞬变幅度增加，与GK大鼠相比，GK-蔗糖组心肌细胞Ca(2+)瞬变幅度降低。编码各种心肌蛋白的基因表达模式的细微变化与GK T2DM和喂食富含蔗糖饮食的对照大鼠心室肌细胞缩短和细胞内Ca(2+)转运的变化有关。
