Mechanisms of genetically-determined diabetes resistance and susceptibility in db/db mice

Aims/Hypothesis: Leptin receptor-deficient db/db mice are a commonly used research model and it is known that the genetic background, on which the mutation is bred, modulates the mice's phenotype. While diabetes-resistant strains exhibit persistent hyperinsulinemia, susceptible backgrounds show progressive hyperglycemia and islet involution. The primary mechanisms of this phenotypic difference however are not known. Differences in insulin resistance, beta cell function, proliferation and apoptosis possibly contribute. We hypothesized that following the phenotypic divergence between two strains of db/db mice with…