Figure 3.

Comparing healthy and type 2 diabetic phenotypes. In healthy individuals, insulin is produced and secreted by beta-cells in the islets of Langerhans (found in the pancreas) when blood glucose levels are above 5mM. Beta-cells are the most abundant cell type in the islets (~70%) and alpha-cells (responsible for glucagon secretion) are the second most abundant (~20%). Insulin then binds to the insulin receptor (IR), which allows uptake of glucose into tissues by inducing translocation of GLUT4 receptors from intracellular vesicles to the plasma membrane. GLUT4 is primarily found in adipose tissue as well as skeletal and cardiac muscle. Glucose is then transported into the cell by GLUT4 from the bloodstream and catabolised in the cell for ATP production, which provides the fuel for intracellular processes, or glucose can be converted to either glycogen or fat for fuel storage after uptake. In individuals with T2D, many islet beta-cells have undergone apoptosis and the function of the surviving cells is impaired, which results in markedly reduced insulin levels in circulation. Additionally, peripheral tissue insulin resistance impairs the action of insulin, resulting in reduced uptake of glucose from circulation, as a result of decreased GLUT4 translocation to the membrane. Reduced insulin levels and action result in hyperglycaemia and hyperlipidaemia, and subsequent T2D associated symptoms manifest in the patient. Inappropriate glucagon secretion, diminished incretin hormone action, increased proinsulin secretion, impaired pancreatic islet neural regulation, and islet amyloid deposition are also characteristic of T2D. This figure and information in its legend are with data adapted from these studies.^{105,106,111,326–328}