Do Pancreatic Alpha Cells Control their Own Secretion or Follow the Orders of Other Cells?

Series: 
Job Candidate Talk
Thursday, January 29, 2015 - 11:05
1 hour (actually 50 minutes)
Location: 
Skiles 006
,  
NIH
,  
Diabetes is a disease of poor glucose control.  Glucose is controlled by two hormones that work in opposite directions: insulin and glucagon. Pancreatic beta-cells release insulin when blood glucose is high, while pancreatic alpha-cells secrete glucagon when blood glucose is low. Both insulin and glucagon secretion are disregulated in people with diabetes. In these people, not enough insulin is secreted in response to elevated glucose levels, while the problem with glucagon secretion is two-fold: too much glucagon is secreted at high glucose levels, while not enough is secreted at low glucose levels. So far, the treatment of diabetes has focused solely on increasing insulin secretion from beta-cells. Therefore, understanding glucose regulated glucagon secretion may lead to new therapies for those with diabetes.There is an ongoing debate as to whether glucose suppresses glucagon secretion directly through an intrinsic mechanism, within the alpha-cell, or indirectly through an extrinsic mechanism. I developed a mathematical model of glucagon secretion in alpha-cells and use it to show that they can control their own secretion. However, experimental evidence shows that factors secreted by pancreatic beta- and delta- cells can also affect glucagon secretion. Therefore, I created the BAD model for pancreatic islets which contains one representative cell of each type and the cellular interactions between them. I use this model to show that these paracrine effects suppress alpha-cell heterogeneity and suggest that delta-cells play a more important role in this than beta-cells.