Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker

Abstract

BackgroundDiabetic 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.MethodsTwo 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.ResultsThe 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.ConclusionsThis 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.

Excess perigestational folic acid exposure induces metabolic dysfunction in post-natal life

“…As cardiac hypertrophy is an important feature of diabetic cardiomyopathy (DCM) (Nunes et al 2013), we speculate that perigestational exposure to HFA may program female progeny to develop DCM, increasing the risk of heart failure (Boudina & Abel 2010, Nunes et al 2013. Strikingly, hyperglycemia (Murarka & Movahed 2010), hyperinsulinemia (Boudina & Abel 2010, Murarka & Movahed 2010, and adiponectin deficiency (Guo et al 2013), all manifested in HFA female offspring, have been suggested to contribute to cardiac hypertrophy (Guo et al 2013).…”

Glucose and Lipid Dysmetabolism in a Rat Model of Prediabetes Induced by a High-Sucrose Diet

“…Furthermore, the impact of the HSu diet on leptin serum levels and on leptin receptor expression would be of interest. Overall, our study shows that nine week of HSu-diet, which mimics at least in part Western diets [10,11,47], can lead to impaired hepatic glucose and lipid metabolism, typical features of T2DM, already present in this prediabetic model, even in the absence of obesity. This animal model of diet-induced prediabetes shows reduced glucose tolerance, postprandial hyperglycemia, hyperinsulinemia, reduced insulin sensitivity (resistance), and hypertriglyceridemia, together with impaired gluconeogenesis and lipogenesis ( Figure 8).…”

H3 Relaxin Protects Against Myocardial Injury in Experimental Diabetic Cardiomyopathy by Inhibiting Myocardial Apoptosis, Fibrosis and Inflammation

“…Accumulating evidence suggests that increased oxidative/nitrative stress coupled to the activation of various downstream proinflammatory and cell death pathways plays pivotal roles in the development of complex biochemical, mechanical and structural alterations that are associated with DCM [33, 34]. However, despite this accumulated knowledge, treatments for DCM remain poor.…”