Insulin resistance: definition and consequences

Insulin resistance is defined clinically as the inability of a known quanit y of exogenous or endogenous insulin to increase glucose uptake and utiliza tion in an individual as much as it does in a normal population. Insulin ac tion is the consequence of insulin binding to its plasma membrane receptor and is transmitted through the cell by a series of protein-protein interact ions. Two major cascades of protein-protein interactions mediate intracellu lar insulin action: one pathway is involved in regulating intermediary meta bolism and the other plays a role in controlling growth processes and mitos es. The regulation of these two distinct pathways can be dissociated. Indee d, some data suggest that the pathway regulating intermediary metabolism is diminished in type 2 diabetes while that regulating growth processes and m itoses is normal. - Several mechanisms have been proposed as possible cause s underlying the development of insulin resistance and the insulin resistan ce syndrome. These include: (1) genetic abnormalities of one or more protei ns of the insulin action cascade (2) fetal malnutrition (3) increases in vi sceral adiposity. Insulin resistance occurs as part of a cluster of cardiov ascular-metabolic abnormalities commonly referred to as "The Insulin Resist ance Syndrome" or "The Metabolic Syndrome". This cluster of abnormalities m ay lead to the development of type 2 diabetes, accelerated atherosclerosis, hypertension or polycystic ovarian syndrome depending on the genetic backg round of the individual developing the insulin resistance. - In this contex t, we need to consider whether insulin resistance should be defined as a di sease entity which needs to be diagnosed and treated with specific drugs to improve insulin action.