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Am J Physiol Regul Integr Comp Physiol (January 30, 2008). doi:10.1152/ajpregu.00749.2007
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Submitted on October 16, 2007
Accepted on January 26, 2008

A Novel Minimal Model to describe NEFA Kinetics following an Intravenous Glucose Challenge

Ray C. Boston1* and Peter J. Moate2

1 Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Pennsylvania, Pennsylvania, United States
2 School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, United States

* To whom correspondence should be addressed. E-mail: drrayboston{at}yahoo.com.

The dynamics of non-esterified fatty acid (NEFA) metabolism in humans requires quantification if we are to understand the etiology of such diseases as type 1 and 2 diabetes as well as metabolic syndrome and obesity. We present a new compartmental model that employs the pattern of plasma glucose concentrations in healthy young adults, to predict the dynamic changes that occur in plasma NEFA concentrations during either a glucose only intravenous glucose tolerance test (GO-FSIGT), or an insulin modified intravenous tolerance test (IM-FSIGT) or a modified protocol (IM-FSIGT-CLAMP) during which variable rate glucose infusions were administered to prevent plasma glucose from declining below 100 mg/dL. The model described all of the major features of the NEFA response to an IVGTT including, an initial latency phase, a phase during which plasma NEFA concentrations plummet to a nadir, and a rebound phase during which plasma NEFA concentrations may rise to a plateau concentration which may be substantially higher than the initial basal NEFA concentration. This model is consistent with physiological processes and provides seven adjustable parameters that can be used to quantify NEFA production (lipolysis) and utilization (oxidation). When tested on data from the scientific literature, the range in estimated rate of lipolysis was 24 - 36 µmol/l/min and for NEFA oxidation rate, 25 - 54 µmol/l/min. All model parameters were well identified and had coefficients of variation less than 15 percent of their estimated values. It is concluded that this model is suitable to describe NEFA kinetics in human subjects.




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R. C. Boston and P. J. Moate
NEFA minimal model parameters estimated from the oral glucose tolerance test and the meal tolerance test
Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R395 - R403.
[Abstract] [Full Text] [PDF]




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