Defining the Molecular and Physiological Mechanisms of Pancreatic Islet Cell Dysfunction Which Lead to Type 2 Diabetes

Defects in insulin secretion are central to the pathogenesis of type 2 diabetes (T2D) but the molecular basis and physiological consequences of those defects are poorly understood, impeding efforts to develop novel therapeutic approaches. Key questions remain unanswered, such as the extent to which T2D-associated islet dysfunction reflects endogenous defects in beta-cell mass or function, as opposed to disruption of external factors impinging on the beta-cells, such as incretins. Recently the investigators have identified several genetic variations (DNA changes) associated with the production and processing of insulin in non-diabetic individuals and now aim to explore in more detail the role of these genetic variations. Utilising a "recruit by genotype" approach, they will identify individuals with and without genetic variants of interest from existing databases of research volunteers. The investigators will collect detailed medical history and measurements, fasted and stimulated blood samples for the profiling of insulin-related hormones and metabolites. The resulting genetic and non-genetic data will be used to improve understanding of the role of genetic variation on insulin secretion and sensitivity defects that lead to the development of T2D.