The effect of oral-hypoglycaemic drugs and obesity on insulin receptor binding

Abstract

This thesis is concerned with the regulation of insulin receptors, with respect to receptor number, affinity and certain postreceptor effects of insulin action. The Aston obese hyperglycaemic (ob/ob) mouse was used as an animal model of obesity and type 2, NID diabetes mellitus. Hepatocyte insulin receptor number and soleus muscle insulin binding were reduced in these mice compared to lean litter mates. The rate of insulin stimulated glycogen synthesis was reduced in the obese mouse between 5 and 40 weeks of age. This defect preceeded the appearance of reduced insulin receptor binding at 10 weeks and a defect beyond the insulin receptor is therefore proposed as a primary aetiological factor in the development of insulin resistance in the obese mouse...