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γ-羧化酶抑制对血清骨钙素的影响可能对2型糖尿病大鼠发生糖尿病性心肌病具有部分保护作用。

Effect of gamma-carboxylase inhibition on serum osteocalcin may be partially protective against developing diabetic cardiomyopathy in type 2 diabetic rats.

作者信息

Gamal Sarah Mahmoud, Sadek Nermeen Bakr, Rashed Laila Ahmed, Shawky Heba Mohamed, Gamal El-Din Maha Mohamed

机构信息

Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt

Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.

出版信息

Diab Vasc Dis Res. 2016 Nov;13(6):405-417. doi: 10.1177/1479164116653239. Epub 2016 Aug 2.

DOI:10.1177/1479164116653239
PMID:27488359
Abstract

AIMS

To investigate the possible protective effect of elevated undercarboxylated osteocalcin on diabetic cardiomyopathy mechanisms and risk factors.

METHODS

In all, 32 male rats were divided into four groups: control, diabetic, diabetic warfarin and normal warfarin-treated groups. Isolated heart functions were assessed; fasting serum insulin, glucose and glycosylated haemoglobin, homeostasis model assessment insulin resistance and lipid profile were investigated. Serum undercarboxylated osteocalcin and adiponectin were also measured. In cardiac tissue, malondialdehyde content, acyl-CoA dehydrogenase gene expression, Bax/Bcl2 ratio, sarcoendoplasmic reticulum calcium ATPase and osteocalcin receptor (G protein-coupled receptor family C group 6 member A) genes expression were investigated.

RESULTS

Prophylactic elevation of undercarboxylated osteocalcin was accompanied by improved insulin sensitivity and lipid profile, increased serum adiponectin, upregulated myocardial osteocalcin receptor with preserved left ventricular function, decreased cardiac malondialdehyde content, acyl-CoA dehydrogenase and Bax/Bcl2 ratio.

CONCLUSION

Undercarboxylated osteocalcin was suggested to have protective effects against diabetic cardiomyopathy, possibly through direct action on upregulated G protein-coupled receptor family C group 6 member A and indirectly via adiponectin. These effects may be mediated through antagonizing oxidative stress and apoptosis.

摘要

目的

研究羧化不全骨钙素升高对糖尿病心肌病机制及危险因素的潜在保护作用。

方法

总共32只雄性大鼠被分为四组:对照组、糖尿病组、糖尿病华法林组和正常华法林治疗组。评估离体心脏功能;检测空腹血清胰岛素、葡萄糖、糖化血红蛋白、稳态模型评估胰岛素抵抗及血脂谱。同时测定血清羧化不全骨钙素和脂联素。在心脏组织中,研究丙二醛含量、酰基辅酶A脱氢酶基因表达、Bax/Bcl2比值、肌浆网钙ATP酶及骨钙素受体(G蛋白偶联受体家族C组第6成员A)基因表达。

结果

羧化不全骨钙素预防性升高伴随着胰岛素敏感性和血脂谱改善、血清脂联素增加、心肌骨钙素受体上调、左心室功能保留、心脏丙二醛含量降低、酰基辅酶A脱氢酶及Bax/Bcl2比值下降。

结论

羧化不全骨钙素对糖尿病心肌病具有保护作用,可能通过直接作用于上调的G蛋白偶联受体家族C组第6成员A并间接通过脂联素发挥作用。这些作用可能通过拮抗氧化应激和细胞凋亡来介导。

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