Insulin resistance, a smaller than expected response to a given dose of insulin, 
is associated with many common diseases including, ageing, polycystic ovarian 
disease, syndrome X, cancer, infections, trauma and, most significantly, obesity 
and type 2 diabetes mellitus. The biochemical basis of insulin resistance in 
type 2 diabetes has been the subject of many studies. Earlier studies have 
indicated that quantitative regulation of the insulin sensitive glucose 
transporters (Glut-4) and insulin receptors themselves may contribute to this 
disorder, however, these two factors are probably inadequate to explain the 
extent of insulin resistance. This point also became apparent by the development 
of only mild hyperinsulinaemia in mice with a targeted mutation in the Glut-4 
gene. Studies on postreceptor defects in type 2 diabetes has recently focused on 
the intrinsic catalytic activity of the insulin receptor and downstream 
signalling events. A reduction in tyrosine phosphorylation of both the insulin 
receptor (IR) and the insulin receptor substrate-1 (IRS-1) has been noted in 
both animal and human type 2 diabetes. Importantly, this appears to occur in all 
of the major insulin-sensitive tissues, namely the muscle, fat and liver. It is 
now clear that decreased signalling capacity of the insulin receptor is an 
important component of this disease. I will review some of the potential 
mechanisms underlying this deficiency.