2021 Virtual Undergraduate Research Symposium
2021 Virtual Undergraduate Research Symposium
Insulin Action Models Applied to Glycerol and Glucose Yield Different Dynamics
Insulin Action Models Applied to Glycerol and Glucose Yield Different Dynamics
PROJECT NUMBER: 2 | AUTHOR: Griffin Hampton, Applied Mathematics and Statistics
MENTOR: Cecilia Diniz Behn, Applied Mathematics and Statistics and Melanie Cree-Green, University of Colorado Anschutz Medical Campus
ABSTRACT
In response to a glucose challenge, insulin is released from the pancreas and, under healthy conditions: 1) suppresses lipolysis in adipose tissue to decrease glycerol concentrations, reducing fasting metabolic pathways, and 2) regulates glucose concentrations through actions in muscle and liver. Insulin resistance (IR) occurs when more insulin is required to achieve the same metabolic control, and IR may be tissue-specific. Adipose, liver, and muscle tissue exhibit distinct dose-dependent responses to insulin in multi-phase hyperinsulinemic-euglycemic (HE) clamps, but the HE clamp protocol does not address potential differences in the dynamics of an endogenous insulin response. Adipose tissue undergoes an enzymatic adjustment of hormone-sensitive lipase while muscle glucose control involves a complex set of intracellular signaling. To investigate the dynamics of insulin acting on adipose tissue, we developed a differential-equations based model that describes the coupled dynamics of glycerol concentrations and insulin action during a six-hour oral glucose tolerance test in female adolescents with obesity and significant IR. The dynamics of insulin acting on muscle and liver were described with the oral minimal model applied to glucose data collected under the same protocol. We found that the peak action of insulin on glycerol occurs earlier and more closely follows changes in plasma insulin concentrations compared to insulin action on glucose. These findings suggest that, in our IR population, the dynamics of insulin action show tissue-specific differences. Specifically, the time scales of insulin action on glycerol and glucose, respectively, indicate that adipose tissue responds more quickly to insulin compared to the delayed insulin response observed in muscle and liver tissue. Improved understanding of the tissue-specific dynamics of insulin action may provide novel insights into IR and the progression of metabolic disease.
PRESENTATION
AUTHOR BIOGRAPHY
Griffin Hampton is a junior pursuing a double major in biochemistry and computational & applied mathematics with a minor in public affairs through the McBride Honors program. He is supported by MURF to do research in the Applied Mathematics and Statistics Department with Dr. Cecilia Diniz Behn. He has studied metabolic mathematics for the past five semesters with Dr. Diniz Behn, working to understand how to represent the dynamics of metabolic systems using different mathematical tools. He is passionate about research in metabolism and hopes to pursue an MD. Ph.D. where he can continue to research metabolism and apply his mathematical background.
This is so interesting! I like how you walked through the background for people who aren’t familiar with the topic before going into more depth about your research and what you have been doing to work in this field. Very accessible for a variety of background knowledge.
I’m glad you enjoyed my talk! I think metabolism is quite fascinating and I really hope that I got you excited about the potential mathematics has to unpack elements of metabolism.
Great work, Griffin!
Thank you!
Very well explained and interesting presentation Griffin! Would you expect the glycerol vs insulin action curve to look differently for someone who is not categorized as insulin resistant?
Hi Drake. Thank you for taking a look at my talk. Good question! We are indeed interested to know if the glycerol vs. insulin action phase plots would show the same dynamics in a population of typical glycemic control as observed for this insulin resistant population.
There is an indication that the plot would change to some degree. A model of free fatty acids applied to a population with a less insulin resistant population used a single insulin action compartment coupled to equations for glucose and free fatty acids (Periwal V., et. al., Am. Physio. Soc., 2008). For their population, the dynamics of insulin acting on glucose and free fatty acids were similar enough where it could apply to both free fatty acids and glucose.
I would suspect that the dynamics would still remain different between how insulin acts on glucose and glycerol. While insulin signaling starts at the same receptor protein, the signaling pathway to regulate lipolysis is shorter than the pathway to encourage glucose uptake. I would expect the phase plot to behave fairly similar.
While a change in the phase plots seems likely, I think the overall observation of different dynamics between insulin action on glucose and glycerol to persist.
Griffin, great work! Would you anticipate that the results might vary between female and male test subjects?