Math Biology Seminar: James Johnson

Insulin is an essential hormone that regulates nutrient homeostasis. Insufficient insulin results in diabetes, one of the most prevalent and costly diseases. Although the primary actions of insulin are to induce glucose uptake and metabolism in distant tissues, including muscle, fat and liver, the insulin secreting pancreatic beta-cells contain a high number of insulin receptors and known to respond to the hormone. On a minute-to-minute time-scale, insulin has been reported to have negative feedback effects on its own secretion, and we have data suggesting that the actions of insulin may be context-dependent, potentially depending on the ambient glucose levels (which are primarily controlled by glucose). Insulin has also been reported to have positive effects on its own synthesis and on the survival of the beta-cells over a timescale of months. Within beta-cells, insulin production is inherently stressful and exerts a negative effect on beta-cell proliferation that is most pronounced at a young age. We have also recently found that single beta-cells can exist in ‘bursting’ states of elevated insulin production that account for a significant proportion of the previous described heterogeneity in this cell type. Thus, using a variety of experimental approaches, we seek to understand context-dependent insulin feedback signalling on single beta-cells and their collective populations and we are interested in collaborating to build quantitative and testable models that could be used to explain the pathogenesis of diabetes. We also interested in expanding models to include other tissues and other soluble factors that are also relevant in nutrient homeostasis and diabetes.