Endocrine Abstracts

Insulin resistance, which can be defined as a state of reduced responsiveness to normal circulating levels of insulin, plays a major role in the development of type 2 diabetes. Whilst standard definitions of insulin resistance still define it in terms of insulin’s effects on glucose metabolism, the last decade has seen a shift from the traditional ‘glucocentric’ view of diabetes to an increasingly acknowledged ‘lipocentric’ viewpoint. This hypothesis holds that abnormalities in fatty acid metabolism may result in inappropriate accumulation of lipids in muscle, liver and β-cells and that this lipid accumulation is involved in the development of insulin resistance in muscle and liver as well as impairing β-cell function (so called ‘lipotoxicity’). Interestingly, studies in people with rare forms of extreme insulin resistance have provided a number of significant mechanistic insights pertaining to this ‘lipocentric’ notion of type 2 diabetes and have also begun to yield novel therapeutic targets.