Pathophysiological characterization of the ApoE−/−;db/db mouse: A model of diabetes and atherosclerosis

• The availability of in vivo experimental models accurately replicating the pathophysiological mechanisms of type 2 diabetes and atherosclerosis is essential. • Animal models reproducing these complex disease phenotypes are strongly needed to study the underlying pathophysiological mechanisms, identify therapeutic targets, develop effective treatments and handling strategies, and improve diagnostics. • ApoE −/−;db/db mice develop combined features of diabetes, obesity and accelerated atherosclerosis. • ApoE −/−;db/db mice show increased plasma glucose, glycosylated hemoglobin and glucagon levels, glucose, sodium and albumin excretion and urinary flow, total cholesterol, triglycerides and HDL-cholesterol, left ventricular ejection fraction and a high degree of atherosclerosis. • ApoE −/−;db/db mice constitute a suitable experimental model for the study of type 2 diabetes associated with atherosclerosis, and should be implemented to find underlying mechanisms and new therapeutics. The high prevalence of type 2 diabetes and atherosclerosis makes essential the availability of in vivo experimental models that accurately replicate the pathophysiological mechanisms of these diseases. Apolipoprotein E knockout mice (ApoE -/- ) have been used in atherosclerosis studies, and the db/db mice show hyperphagia and obesity. Mice harbouring both alterations (i.e., ApoE −/−;db/db ) are expected to develop combined features of type 2 diabetes, obesity and accelerated atherosclerosis. To deepen into their pathophysiological profile and further assess their potential as an experimental model, we studied their mortality and their pancreatic, cardiac, and renal phenotype. We analysed during 6 months the glycemic and lipid profile, pancreatic, cardiac and renal structure and function and atherosclerosis in ApoE −/−;db/db mice. ApoE −/−;db/db mice show increases in plasma glucose (although without statistical significance), glycosylated hemoglobin and glucagon levels, total cholesterol, triglycerides and HDL-cholesterol and in both insulin-producing β and glucagon producing α cells, and in the tissue expression of both hormones with respect to control (C57BL/6) mice; they show a remarkably high degree of atherosclerosis, higher left ventricular ejection fraction. Although renal function is normal, glucose, sodium and albumin excretion and urinary flow are increased with respect to control mice. Summarizing, ApoE −/−;db/db mice constitute a suitable experimental model for the study of type 2 diabetes associated with atherosclerosis.