*Geek Box: Pancreatic Beta-Cells
Understanding the role of beta-cells of the pancreas is critical to grasping the pathogenesis of T2DM. While impaired sensitivity to insulin in peripheral tissues, particularly the liver, skeletal muscle and adipose tissues, is an important factor, progression of T2DM is characterised by insufficient secretion of insulin from pancreatic beta-cells, and ultimately, failure of beta-cells to produce and secrete insulin in response to rising blood glucose levels. Insulin secretion from beta-cells is highly sensitive to changes in blood glucose levels, and is characterised by a bi-phasic response: first-phase insulin secretion is an immediate response to an increase in blood glucose following a meal, and is the release of insulin stored in beta-cells, and the second-phase response, which occurs from new insulin synthesised and released during the post-prandial period. In T2DM, glucose-stimulated insulin secretion becomes defective over time, resulting in a loss of the first-phase insulin response. Understanding of the critical role beta-cells has moved T2DM away from a purely glucose-centric view, to greater appreciation for the role of visceral fat in imparting hepatic glucose and fatty acid uptake, and the spillover of fat into the pancreas. While drugs, like sulfonylureas, target insulin secretion, to date the most effective intervention targeting restoration of beta-cell functionality appears to be from Roy Taylor’s research group investigating very-low-calorie-diets [VLCD]. However, it should be stated that there appears to be a time-sensitive component to restoring beta-cell function, as beta-cells decline inexorably over time, i.e., intervention within 5-years of diagnosis may be more efficacious.