Genetic Models of Insulin Resistance and Type 2 Diabetes

Studies can be performed in any commercially available genetic model of insulin resistance or type 2 diabetes including ob/ob mice, db/db mice and Zucker fa/fa or ZDF rats.  These animals develop obesity, insulin resistance and/or diabetes from an early age because of a mutation in a single gene. The mutation in ob/ob mice prevents the production of leptin whereas db/db mice and Zucker rats have marked elevations in circulating leptin but deficient leptin receptors.

All four models display hyperinsulinaemia and are insulin-resistant but differ in the degree of hyperglycaemia. For example, Zucker fa/fa rats are not hyperglycaemic, ob/ob mice exhibit mild to moderate increases in plasma glucose levels whereas db/db mice and ZDF rats are overtly diabetic and display pronounced hyperglycaemia.