|Gene||Location||Size||Size of Coding region||Justification|
|Insulin receptor substrate 1 (IRS-1)||chr9:81585251–81638071||5365 bases||3708 bases||
Low cellular IRS 1 gene and protein expression predict insulin resistance and NIDDM.|
Impairment of insulin-induced glucose uptake by skeletal muscles from high-salt-fed Dahl S rats was neither due to changes in the insulin receptor number, mRNA or binding affinity, nor due to diminished expression of GLUT4 protein. Impairment in the insulin signaling pathway might possibly be downstream of the insulin receptor and upstream of GLUT4, possibly in the IRS-1 and/or IRS-2 signaling molecules.
|Insulin receptor substrate 2 (IRS-2)||chr16:18878139–18889441||24234 bases||3963 bases||Ubiquitin-mediated degradation of IRS1 and IRS2 promotes insulin resistance. IRS2 dysfunction is critical in the development of type 2 diabetes. Insulin was not able to suppress gluconeogenic gene expression in primary hepatocytes lacking IRS-2, but when IRS-2 signaling was reconstituted, these cells recovered this response to insulin.|