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Table 1 Chromosomal location, genomic and protein sizes of IRS-1 and IRS-2 in rats

From: Important genetic checkpoints for insulin resistance in salt-sensitive (S) Dahl rats

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.

  1. Summary of IRS-1 and -2 genes demonstrating their chromosomal location, respective genomic and coding sequence sizes, and known effects of their dysregulation.