Mathematical Modeling Studies for Glucose Metabolism Cedars-Sinai Skip to content Close Select your preferred language English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog English English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog Translation is unavailable for Internet Explorer Cedars-Sinai Home 1-800-CEDARS-1 1-800-CEDARS-1 Close Find a Doctor Locations Programs & Services Health Library Patient & Visitors Community My CS-Link RESEARCH clear Go Close Navigation Links Academics Faculty Development Community Engagement Calendar Research Research Areas Research Labs Departments & Institutes Find Clinical Trials Research Cores Research Administration Basic Science Research Clinical & Translational Research Center (CTRC) Technology & Innovations News & Breakthroughs Education Graduate Medical Education Continuing Medical Education Graduate School of Biomedical Sciences Professional Training Programs Medical Students Campus Life Office of the Dean Simulation Center Medical Library Program in the History of Medicine About Us All Education Programs Departments & Institutes Faculty Directory Diabetes and Obesity Research Institute Back to Diabetes and Obesity Research Institute About Us Research Areas Antipsychotic Drugs and Diabetes Research CB1 Receptor Antagonist and Adipocyte Studies Discovering Genes for Diabetes and Obesity Effects of High Altitude on Diabetes and Obesity Endothelial Dysfunction Impaired Insulin Resistance at the Cell Level Examining the Effects of Sleep Deprivation on Weight Examining the Role of Insulin Clearance During Insulin Resistance Facets of Diabetes and Obesity Research GLP 1 and Gut Brain Communication Research for Obesity and Diabetes Islet Beta Cell Research on Insulin Secretion Mathematical Modeling Studies for Glucose Metabolism Methane Producing Microbes and Obesity Sex-Based Differences Regarding Obesity and Diabetes Weight-Loss Surgeries for Treatment of Obesity and Diabetes Team Research Labs Job Opportunities 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 Polidori D, Mari A, Ferrannini E. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves model-based indices of beta cell function in patients with Type 2 diabetes. Diabetologia. 2014 May;57(5):891-901. http://link.springer.com/article/10.1007%2Fs00125-014-3196-x. Polidori D, Sha S, Mudaliar S, Ciaraldi TP, Ghosh A, Vaccaro N, Farrell K, Rothenberg P, Henry RR. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care. 2013 Aug;36(8):2154-2161. http://care.diabetesjournals.org/content/36/8/2154. Polidori D, Sha S, Ghosh A, Plum-Mörschel L, Heise T, Rothenberg P. Validation of a novel method for determining the renal threshold for glucose excretion in untreated and canagliflozin-treated subjects with Type 2 diabetes mellitus. J Clin Endocrinol Metab. 2013 May;98(5):E867-871. http://press.endocrine.org/doi/abs/10.1210/jc.2012-4205. Sha S, Polidori D, Farrell K, Ghosh A, Natarajan J, Vaccaro N, Pinheiro J, Rothenberg P, Plum-Mörschel L. Pharmacodynamic differences between canagliflozin and dapagliflozin: results of a randomized, double-blind, crossover study. Diabetes Obes Metab. 2015 Feb;17(2):188-197. http://onlinelibrary.wiley.com/doi/10.1111/dom.12418/abstract;jsessionid=F199DAB925F96EAECEEC8A7A735334F9.f02t03. Polidori D, Rowley C. Optimal back-extrapolation method for estimating plasma volume in humans using the indocyanine green dilution method. Theor Biol Med Model. 2014 Jul 22;11:33. http://www.tbiomed.com/content/11/1/33. Liang Y, Arakawa K, Ueta K, Matsushita Y, Kuriyama C, Martin T, Du F, Liu Y, Xu J, Conway B, Conway J, Polidori D, et al. Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models. PLOS One. 2012;7(2):e30555. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0030555. Polidori D, Sha S, Heise T, Natarajan J, Artis E, Wang S-S, Vaccaro N, Rothenberg P, Stirban A. Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on C-peptide kinetics. Clinical Pharm in Drug Dev. 2015 Jan-Feb;4(1):12-17. http://onlinelibrary.wiley.com/doi/10.1002/cpdd.115/abstract. Sha S, Devineni D, Ghosh A, Polidori D, Hompesch M, Arnolds S, Morrow L, Spitzer H, Demarest K, Rothenberg P. Pharmacodynamic effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, from a randomized study in patients with Type 2 diabetes. PLOS One. 2014 Sep 30;9(9):e110069. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0110069. Stein P, Berg JK, Morrow L, Polidori D, Artis E, Rusch S, Vaccaro N, Devineni D. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces post-meal glucose excursion in patients with Type 2 diabetes by a non-renal mechanism: results of a randomized trial. Metabolism. 2014 Oct;63(10):1296-1303. http://www.metabolismjournal.com/article/S0026-0495(14)00198-X/abstract. Rosenstock J, Aggarwal N, Polidori D, Zhao Y, Arbit D, Usiskin K, Capuano G, Canovatchel W; Canagliflozin DIA 2001 Study Group. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with Type 2 diabetes. Diabetes Care. 2012 Jun;35(6):1232-1238. http://care.diabetesjournals.org/content/35/6/1232. Klein P, Polidori D, Twito O, Jaffe A. Impaired decline in renal threshold for glucose during pregnancy: a possible novel mechanism for gestational diabetes mellitus. Diabetes Metab Res Rev. 2014 Feb;30(2):140-145. http://onlinelibrary.wiley.com/doi/10.1002/dmrr.2474/abstract. Devineni D, Curtin CR, Polidori D, Gutierrez MJ, Murphy J, Rusch S, Rothenberg PL. Pharmacokinetics and pharmacodynamics of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in subjects with Type 2 diabetes mellitus. J Clin Pharmacol. 2013 Jun;53(6):601-610. http://onlinelibrary.wiley.com/doi/10.1002/jcph.88/abstract. Have Questions or Need Help If you have questions or would like to learn more about the Diabetes and Obesity Research Institute at Cedars-Sinai, please call or send us a message. 8700 Beverly Blvd. Thalians Health Center, Room E104 Los Angeles, CA 90048 310-967-2795 Fax:310-967-3869 SEND A MESSAGE Please ensure Javascript is enabled for purposes of website accessibility