Metabolic programming of insulin action and secretion

Abstract

Type 2 diabetes (T2D), also known as non-insulin dependent diabetes mellitus, arises as a consequence of peripheral insulin resistance in combination with an inability of pancreatic islet β-cells to secrete adequate amounts of insulin. It is widely recognized that the current environment (e.g. an unhealthy diet and sedentary lifestyle) contributes to this process. In recent years, however, the role of the early environment, particularly nutrition, has emerged as an important factor capable of influencing health and disease risk of an individual, including risk of T2D. The impact of early environment on glucose metabolism has been extensively studied. Compelling evidence from epidemiological studies and animal models suggests that early nutrition can affect insulin action as a mediator of glucose homeostasis in peripheral tissues and as an important regulator of appetite and body weight. The early environment can also affect β-cell mass and function, and hence insulin secretion. The molecular mechanisms underlying the relationship between a suboptimal early environment and impaired insulin action and secretion is thought to include epigenetic modifications of the foetal genome, oxidative stress and mitochondrial dysfunction.