It is a generally held view that obesity-related type 2 diabetes develops as a consequence of failure of islet b-cell compensation for insulin resistance. This is more likely to develop if the islets have an underlying genetic and/or acquired susceptibility to failure. Implicit in this view is that insulin resistance comes first, as a consequence of poor lifestyle, overweight and obesity, and b-cell compensation and failure follows. If this is correct, the islet b-cell is a victim to insulin resistance.
An alternative view places the islet b-cell more in a primary role or as the perpetrator. The hyper-responsiveness of genetically predisposed islet b-cells to nutrient-induced stress results in hyperinsulinaemia that favours weight gain and insulin resistance. A hyperinsulinaemia/insulin resistance viscious cycle results, which is followed by the development of metabolic syndrome and its related conditions of non-alcoholic fatty liver disease, polycystic ovarian syndrome, type 2 diabetes and cardiovascular disease.
Focus of this symposium talk will be on reviewing the evidence from the literature and our laboratory for this alternative view that places the islet b-cell as the perpetrator. If this alternative view is substantiated, a paradigm shift in prevention and treatment strategies for obesity-related type 2 diabetes and the conditions of metabolic syndrome may be warranted. The the key objective would then be to develop therapies that attenuate the islet b-cell’s hyper-responsiveness to stress such as that caused by an adverse nutrient supply.