Insulin receptor (IR) and insulin-responsive glucose transporter (Glut4) represent two candidate genes involved in the development of non-insulin dependent diabetes mellitus (NIDDM); detection of molecular alterations in these genes might explain their possible contribution to NIDDM.
A genetic analysis of diabetic and non-diabetic Punjabi Sikhs (n = 164) was made for markers of non-insulin-dependent diabetes mellitus using insulin receptor, insulin, and HLA-D alpha chain gene probes.
Although no significant association of restriction fragment length polymorphism with Type 2 diabetes was found in the present study, our results suggest that the restriction fragment length polymorphism in the human insulin receptor gene varies among ethnic groups, and that the restriction fragment length polymorphism linked to the human insulin receptor gene might be a useful marker for the linkage study of the genes located close to the human insulin receptor gene on chromosome 19.
An asymmetrical reduction in the levels of the insulin receptor mRNA transcribed from one allele was reported in some patients with severe insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM).
Associations between type 2 diabetes (and/or parameters contributing to glucose homeostasis) and genetic variation in the genes encoding insulin receptor substrate (IRS)-1 and -2 have been reported in several populations.
Because NIDDM is heterogeneous and perhaps polygenic in nature, these linkage analyses in families with NIDDM can be extended to other genes when they are cloned such as that coding for the insulin receptor.
Because the nature and location of the insertion did not suggest a role in insulin-receptor function, the association of this RFLP with NIDDM and hyperinsulinemia was reexamined in a small sample of Whites.
Beyond these physiological roles of insulin, a shared feature between the periphery and CNS is that decreases in insulin receptor activity and signaling (i.e. insulin resistance) contributes to the pathological consequences of type 2 diabetes (T2DM) and obesity.