Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker
Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker
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DOI：
10.1186/1475-2840-12-44
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发表时间：
2013-03-07
影响因子：
9.3
通讯作者：
Reis, Flavio
中科院分区：
文献类型：
--
作者：
Nunes, Sara;Soares, Edna;Reis, Flavio
背景资料：糖尿病性心肌病（DCM）是由糖尿病（DM）引起的代谢和细胞异常引起的心肌结构和功能改变。糖尿病前期疾病对心脏组织的影响仍有待阐明。本研究的目的是阐明是否心脏功能障碍已经存在于糖尿病前期的状态，在胰岛素抵抗的存在下，并解开潜在的机制，在大鼠模型中没有肥胖和高血压作为混杂因素。高蔗糖（HSu）饮食组（n = 7）-接受35%蔗糖的饮用水的大鼠与载体对照组（n = 7）。动物模型的特征在于体重（BW）和血糖，胰岛素血和糖尿病概况。评估以下参数以评估可能的早期心脏改变和潜在机制：血压、心率、心脏和左心室（LV）营养指数，以及纤维化、肥大、增殖、凋亡、血管生成、内皮功能、炎症和氧化应激标志物的血清和组织蛋白和/或mRNA表达。Hsu组大鼠空腹血糖正常，糖耐量减低，伴有高胰岛素血症和胰岛素抵抗（P < 0.01），证实该模型为糖尿病前期。此外，虽然观察到高血脂症（P < 0.05），但没有肥胖和高血压。关于HSu饮食对心脏组织的影响，我们的结果表明，9周的治疗可能与初始心脏变化有关，如LV重量/BW比值增加所示脑利钠肽（BNP）mRNA高表达（P < 0.01（P < 0.01），以及纤维化、肥大、血管生成和内皮损伤以及氧化应激的其他重要介质的显著上调趋势。炎症和细胞凋亡标记物测量是不变的Conclusions. This糖尿病前期/胰岛素抵抗的动物模型可能是一个重要的工具，以评估早期心脏的影响代谢异常（高胰岛素血症和糖耐量受损与空腹血糖正常），没有混杂因素，如肥胖和高血压。左心室肥厚已经存在，脑钠肽似乎是这种情况下最好的早期标志物。
Background: Diabetic cardiomyopathy (DCM) is defined as structural and functional changes in the myocardium due to metabolic and cellular abnormalities induced by diabetes mellitus (DM). The impact of prediabetic conditions on the cardiac tissue remains to be elucidated. The goal of this study was to elucidate whether cardiac dysfunction is already present in a state of prediabetes, in the presence of insulin resistance, and to unravel the underlying mechanisms, in a rat model without obesity and hypertension as confounding factors.Methods: Two groups of 16-week-old Wistar rats were tested during a 9 week protocol: high sucrose (HSu) diet group (n = 7) - rats receiving 35% of sucrose in drinking water vs the vehicle control group (n = 7). The animal model was characterized in terms of body weight (BW) and the glycemic, insulinemic and lipidic profiles. The following parameters were assessed to evaluate possible early cardiac alterations and underlying mechanisms: blood pressure, heart rate, heart and left ventricle (LV) trophism indexes, as well as the serum and tissue protein and/or the mRNA expression of markers for fibrosis, hypertrophy, proliferation, apoptosis, angiogenesis, endothelial function, inflammation and oxidative stress.Results: The HSu-treated rats presented normal fasting plasma glucose (FPG) but impaired glucose tolerance (IGT), accompanied by hyperinsulinemia and insulin resistance (P < 0.01), confirming this rat model as prediabetic. Furthermore, although hypertriglyceridemia (P < 0.05) was observed, obesity and hypertension were absent. Regarding the impact of the HSu diet on the cardiac tissue, our results indicated that 9 weeks of treatment might be associated with initial cardiac changes, as suggested by the increased LV weight/BW ratio (P < 0.01) and a remarkable brain natriuretic peptide (BNP) mRNA overexpression (P < 0.01), together with a marked trend for an upregulation of other important mediators of fibrosis, hypertrophy, angiogenesis and endothelial lesions, as well as oxidative stress. The inflammatory and apoptotic markers measured were unchanged.Conclusions: This animal model of prediabetes/insulin resistance could be an important tool to evaluate the early cardiac impact of dysmetabolism (hyperinsulinemia and impaired glucose tolerance with fasting normoglycemia), without confounding factors such as obesity and hypertension. Left ventricle hypertrophy is already present and brain natriuretic peptide seems to be the best early marker for this condition.