The Banting Memorial Lecture 2011: Hyperinsulinaemia – Cause or Consequence? Barbara Corkey; ADA 2011.

Globalization and changes in diet and lifestyle have led in the past half-century to a dramatic change in the metabolic diseases faced by people. The additives that go into much of the food consumed have never been formally assessed for effect on health.

There is evidence to suggest that hyperinsulinaemia itself may be a contributor to insulin resistance thus stimulating a vicious spiral of leading to diabetes. However, it is known that Free Fatty Acids (FFA) such as MOG can stimulate increased insulin secretion in response to glucose as can artificial sweeteners. Both are found in modern foods. For example saccharin can cause enhanced 48-hour insulin secretion in response to glucose. Iron has a similar effect.

This leads to a question as to whether these non-food compounds cause increased insulin secretion through a direct effect on the pancreas. MOG has not been shown to increase calcium modulated insulin secretion in beta cells, but appears to generate this effect through generation of reactive oxidation species (ROS) in the mitochondria in pancreas. This is known to increase oxidative stress and therefore potentially damage in cells. The biological benefit of this mechanism is that increased ROS also occurs in the presence of normal food substrates and therefore allows their metabolism. Indeed the addition of ROS scavengers reduces basal insulin secretion, thus food stimulated ROS is a necessary component in insulin secretion. However the addition of non-food compounds to modern food leads to an unnecessary ROS generated increase in insulin. Red wine acts as a minor ROS scavenger and thus reduces MOG induced, ROS stimulated insulin secretion in trials. LC-CoA stimulates insulin secretion by FFA, and it has been shown that inhibition of LC-CoA reduces insulin secretion. The exact effect of MOG and other food additives on this pathway is not yet clear.

Thus there seems to be a clear link between Redox status between the cytosol and mitochondria and insulin secretion.

Increased redox in adipocytes is also noted in circumstances that increase insulin secretion and leads to lipid synthesis. Scavenging ROS reduces lipid deposition and suggest that there is a common factor that links insulin secretion and insulin resistance, which is independent of hyperglycaemia – in other words changes in ROS and Redox, may lead to both insulin resistance and hyperinsulinaemia.

In conclusion there is emerging evidence that alterations in redox due to dietary content may be more influential in the causation of insulin resistance than was previously supposed. In addition similar mechanisms may independently trigger increased insulin secretion. This leads to the hypothesis that it may be dietary factors and not hyperinsulinaemia alone that cause insulin resistance and ultimately type-2 diabetes. Further research in this field is needed and in particular a clear understanding of the full impact that modern foodstuffs may be causing should be developed.