Lipid mediators and inflammation in glucose intolerance and insulin resistance

Clinical and epidemiological studies suggest that patients who are overweight or obese are at greater risk to develop glucose intolerance and insulin resistance leading to type II diabetes and cardiovascular disease. Despite many hypotheses, it has been difficult to pin-point the precise causes of insulin resistance or impaired glucose tolerance. This commentary aims to stimulate debate by providing some mechanistic insights into a unifying hypothesis by which disturbed lipid metabolism, increased circulating lipid-derived mediators and excess accumulation of toxic lipid metabolites in adipose, muscle, liver and pancreatic beta cells contribute to inflammation, insulin resistance and beta cell dysfunction in type II diabetes. This understanding will direct future drug discovery research to identify and develop novel compounds that can regulate both metabolic and immune/inflammatory systems to provide a dual strategy to combat metabolic disease, especially insulin resistance and type II diabetes.