Diabetes in Mice with Monogenic Obesity: The db/db Mouse and Its Use in the Study of Cardiac Consequences

Abstract

The leptin receptor deficient db/db mouse has served as a rodent model for obesity and type 2 diabetes for more than 40 years. Diabetic features in db/db mice follow an age-dependent progression, with early insulin resistance followed by an insulin secretory defect resulting in profound hyperglycemia. Diabetic db/db mice have been utilized to assess the cardiac consequences of diabetes, specifically evidence for a distinct diabetic cardiomyopathy. The db/db model is characterized by a contractile function deficit in the heart which becomes manifest 8-10 weeks after birth. Metabolic changes include an increased reliance on fatty acids and a decreased reliance on glucose as a fuel source for oxidative metabolism within the heart. As a mouse model for type 2 diabetes, both drug treatment and transgenic manipulation have proven beneficial towards improving metabolism and contractile function. The db/db mouse model has provided a useful resource to understand and treat the type 2 diabetic condition.