Q&A: insulin secretion and type 2 diabetes: why do β-cells fail?
What is type 2 diabetes? Diabetes mellitus is a term that covers a multitude of problems with many etiologies, unified by one common feature: the pathological elevation of blood glucose. Sustained hyperglycemia leads to tissue damage in susceptible organs and eventually results in secondary complications including retinopathy, nephropathy, peripheral neuropathy, cardiovascular disease and stroke [1-3]. Diabetes currently affects 387 million people worldwide, and this number is predicted to increase to 592 million by 2035 [4]. The dramatic rise in the disease in recent years not only causes individual misery, but also places an enormous and increasing burden on healthcare systems and the global economy [5,6]. Indeed, many countries spend as much as 10 % of their healthcare budget on treating diabetes and its complications. Type 2 diabetes (T2D) is the most common form of the disease, accounting for approximately 90 % of cases [6]. It has a strong genetic component that is amplified by factors such as age, obesity, diet, physical activity and pregnancy. T2D is characterized by insufficient secretion of insulin from the β-cells of the pancreatic islets, coupled with impaired insulin action in target tissues such as muscle, liver and fat (a condition termed insulin resistance). Hyperglycemia results when insulin secretion is unable to compensate for insulin resistance [7]. Insulin resistance is increased during obesity, which explains, at least in part, why T2D risk is enhanced by obesity. The regulation of glucose homeostasis by insulin is summarized in Fig. 1. Type 1 diabetes (T1D) is much less common than T2D, accounting for <10 % of cases. It is precipitated by an autoimmune attack on the β-cells that results in an insulin deficient state, although a small number of functioning β-cells may remain [8]. Typically, T1D presents in childhood or young adulthood.