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Alina Scridon, Marcel Perian, Alina Marginean, Ciprian Fisca, Adriana Vantu, Doina Ghertescu, Philippe Chevalier and Razvan Constantin Serban


Background: Experimental models are essential for clarifying the pathogenesis of diabetes mellitus (DM). We aimed to provide an exhaustive description of clinical, biochemical, and hematologic features of rats with streptozotocin (STZ)-induced DM.

Methods: Wistar rats were assigned to control (n=14) or DM (n=17) groups. DM was induced using STZ (60 mg/kg, i.p.). If STZ failed to induce DM, rats were reinjected with a similar STZ dose. Bodyweight, 24-h food and water intake were measured weekly during 28 weeks. At the end of the study lipid profile, kidney function, and complete blood count were assessed.

Results: STZ induced DM in 58.82% of rats. The second STZ administration induced DM in 71.43% of the remaining rats. Diabetics presented progressive, but less significant bodyweight increase than controls, and higher food and water consumption. At the end of the study, diabetics presented higher white blood cells count, glucose, triglycerides, total and low-density lipoprotein cholesterol, and lower creatinine clearance than controls (all p≤0.02). No significant difference was observed between diabetics injected once and those that were reinjected, in any of the studied parameters.

Conclusions: This study provides one of the longest follow-ups of rats with STZ-induced type 1 DM, demonstrating that the STZ-diabetic rat replicates the most relevant clinical, biochemical, and hematologic features of human diabetes. The present data also indicate, for the first time, that rats with initial unsuccessful STZ administration can be safely reinjected, with outcomes similar to those seen in rats receiving a single injection.

Open access

Alina Scridon, Emmanuelle Fouilloux-Meugnier, Emmanuelle Loizon, Marcel Perian, Sophie Rome, Claude Julien, Christian Barrès and Philippe Chevalier


Background: Aging is associated with significantly increased prevalence of cardiac arrhythmias, but transcriptional events that underlie this process remain to be established. To gain deeper insight into molecular mechanisms of aging-related cardiac arrhythmias, we performed mRNA expression analysis comparing atrial and ventricular myocardium from Wistar-Kyoto (WKY) rats of different ages. Methods: Atrial and ventricular sampling was performed in 3 groups (n=4 each) of young (14-week-old), adult (25-week-old), and aging (47-week-old) WKY rats. mRNA expressions of 89 genes involved in cardiac arrhythmogenicity were investigated using TaqMan Low Density Array analysis. Results: Of the 89 studied genes, 40 and 64 genes presented steady atrial and ventricular expressions, respectively. All genes differentially expressed within the atria of WKY rats were up-regulated with advancing age, mainly the genes encoding for various K+, Ca2+, Na+ channels, and type 6 collagen. Atrial expression levels of 19 genes were positively correlated with age. Ventricular transcriptomic analysis revealed a balance between up-regulated and down-regulated genes encoding for the same ion channels. Conclusion: Our results indicate the induction of an up-regulation transcriptional response in atrial but not ventricular myocytes with advancing age, suggesting that the two chambers undergo different molecular remodeling programs. Aging atria displayed a transcriptomic profile consistent with higher propensity to arrhythmias, including up-regulation of genes encoding for If, ICa-L, ICa-P, INa, outward K+ currents, and collagen, while ventricular transcriptome did not seem to be significantly altered by aging. These observations could explain the higher propensity to atrial than ventricular arrhythmias in the elderly.