Modeling of beta-cell Metabolic Activity and Islet Function : a Systems Approach to Type II Diabetes

Abstract: Diabetes has gained growing attendance as one of the key non communicable diseases (NCD) with the World Health Organization identifying it as the focus of the World Health Day 2016. It is reported that more than 420 million people suffer from diabetes, a number predicted to rise in the coming years. This report forms part of a broader, long term focus project that aims to establish a systems approach to type 2 diabetes (T2D), the variant that accounts for more than 90% of reported diabetes cases. The broader project objectives are to identify possible biomarkers for the onset and the progression of T2D as a precursor to enable potential future approaches to delay onset, or even reverse disease states, via active bio-compounds and/or establishment of beneficial nutritional patterns. The 6-month master’s work reported here is sub-project that focused specifically on cell level vesicle trafficking processes. These processes are believed to be crucial in understanding the formation amyloid plaques, which compromise or kill the insulin secreting beta cells. Up until now, there has been a lack of appropriate experimental techniques to directly observe this process in live cells.  Hence we have developed 2 new techniques: (i)               a method of imaging the actin and tubulin network reorganization during exocytosis of the insulin containing granules while exploring novel ways of characterizing the network. (ii)             a method of imaging the granules themselves and using particle tracking microrheology to analyze their movement patterns during stimulation with glucose. These new techniques open the door to follow up experiments which would allow development of a cell scale mathematical model or simulation correlating short term glucose dynamics to risk of amyloid plaque formation and T2D.