Grant: China-Canada Joint Health Research Initiative

Excess supply of nutrient fuels, viz., carbohydrates, proteins and fats, can lead to toxicity by disturbing the normal cellular functions in the body, resulting in obesity and diabetes. Thus, continuous exposure of pancreatic beta cells to high fat and glucose causes their failure to produce insulin in response to changes in blood glucose concentrations. In the whole body other tissues also do not respond normally to insulin and cannot effectively use blood glucose under conditions of excess fuel supply. These toxic effects of excessive fuels can be due to reduced useable energy production, production of mis-folded proteins and elevated production of harmful free radicals. It is particularly important to understand about the way the cells escape from the toxicity of excess fuels in conditions like obesity and diabetes, which are often associated with fuel oversupply. In the present proposal, we are proposing that the well-known anti diabetic drugs metformin and berberine act by reducing the toxic effects of nutrient fuels. We plan to investigate how these drugs help beta cells of pancreas to handle excess fuels. We also plan to examine if these two anti-diabetic drugs reduce the fuel toxicity in the body tissues and make these tissues to become more sensitive to insulin. We will investigate the details of the fuel detoxification that is brought about by metformin and berberine in the beta cells and in other body tissues like liver, muscle and adipose tissue. The information obtained from these studies will help in understanding the importance of fuel detoxification as a way of treating diabetes and obesity.