Type 2 Diabetes: What Went Wrong with Insulin?

Abstract

Type 2 diabetes mellitus, or non-insulin dependent diabetes mellitus (NIDDM), is a pathological condition characterized by an inadequate response to insulin, a hormone responsible for regulating blood glucose levels. NIDDM comprises of 90-95% of all cases of diabetes.¹

Normally, insulin is released by pancreatic beta cells into the bloodstream, acting on receptors found in tissues such as skeletal muscle and the liver.² The binding of insulin to insulin receptors stimulates glucose uptake into cells and the storage of glucose as glycogen (glycogenesis).³ Evidence suggests that genetic mutations may increase susceptibility to NIDDM. Specifically, a reduction of insulin receptor gene expression may be partly responsible for insulin resistance in NIDDM.⁴ While molecular pathways are not very well understood, evidence suggests high blood fatty acid levels may inhibit insulin receptor substrates (IRS) in the insulin-signalling cascade.⁴

The isoforms of the glucose transporters (GLUTs) primarily involved in diabetes are GLUT2 and GLUT4.⁵ There is currently limited data linking specific genes to diabetic pathology, warranting for genome-wide analyses.⁶ Despite an increasing prevalence of diabetes, there is encouraging evidence supporting the ability of exercise to reduce insulin resistance.⁷