Mathematical Modeling Studies for Glucose Metabolism

Mathematical and statistical models are powerful research tools used by scientists at the Cedars-Sinai Diabetes and Obesity Research Institute (DORI). Richard Bergman, PhD, and colleagues have extensive experience developing and applying mathematical models in combination with experiments to gain insights into Type 2 diabetes physiology.

Currently, mathematical modeling is used by researchers at DORI to inform studies on the physiology of glucose metabolism. This includes continued application of Bergman’s minimal model of glucose metabolism and further characterization of a recently developed mathematical model on lactate metabolism that, for the first time, has enabled in vivo estimation of glucokinase (GK) activity.

David Polidori, PhD, senior director in translational medicine at Janssen Research and Development, is currently a visiting scientist at DORI. Polidori was a member of the team that developed canagliflozin, the first SGLT2 inhibitor approved by the FDA for the treatment of Type 2 diabetes. During the development of canagliflozin, Polidori developed and applied a number of mathematical model-based methods for characterizing the effects of canagliflozin on SGLT2- and SGLT1-mediated glucose transport, including developing and validating a new method for determining the renal threshold for glucose excretion based on easily collected clinical data.

Current research at Cedars-Sinai includes:

  • Further experimental and modeling work to better understand insulin-independent effects of glucose on metabolism
    • Novel experimental protocols to directly measure glucose effectiveness and the contribution of different tissues/pathways to whole-body glucose effectiveness
    • Studies to characterize the compensatory metabolic changes that occur in response to SGLT2-inhibitor-mediated reductions in plasma glucose
    • Further validation and characterization of the recently developed model of lactate metabolism

Previous research