Effect of age on hepatocyte and soleus muscle insulin receptor binding in lean and genetically obese diabetic (ob/ob) mice.

Hepatocyte and soleus muscle insulin binding and the rate of insulin stimulated glycogen synthesis were examined in normal lean and genetically obese diabetic (ob/ob) mice with age. In ob/ob mice a significant decrease in the concentration of high affinity hepatocyte insulin receptors and insulin binding to soleus muscle at 10-20 and 10-40 weeks of age respectively was associated with an age related development of insulin resistance characterized by increased body weight, plasma insulin and plasma glucose. In lean mice a significant reduction in the concentration of low affinity hepatocyte receptors and soleus muscle insulin binding was observed at 60 weeks and associated with a marginally increased plasma insulin concentration and unchanged level of glycaemia. Insulin stimulated glycogen synthesis was unchanged with age in lean mouse soleus muscle but in ob/ob was significantly reduced by 5 weeks and preceded the reduction in insulin binding in this tissue. In 40 week ob/ob mice insulin sensitivity was improved and characterized by a reduction in body weight, plasma insulin and glucose, increased hepatocyte high affinity insulin receptor concentration and decreased affinity, Ke. Although insulin binding to soleus muscle was not increased and there was no improvement in insulin stimulated glycogen synthesis at this age, the increased hepatocyte insulin binding was probably not the primary cause of the improved insulin sensitivity which was most likely mediated at post-receptor loci.