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In an earlier paper (Cohen and Bergman, Am. J. Physiol. 268 (1995) E397), we explored the relationship between the exponents in the exponential curve fit to isotopic enrichment versus time and the fractional turnover rate of the largest metabolic pool in the pathway. Here we present the analysis on a more rigorous footing and apply it to questions of cerebral and cardiac metabolism. Our emphasis in this paper is to describe and justify mathematically an approach for analysis of metabolic dynamics, not with the intention of replacing the use of numerical software for estimation of flux rates but for giving the scientist the opportunity to examine the system in an approximate manner, and thereby to check not only that the results of the numerical solution are the correct solutions to the equations but also that the equations portray the correct simplification of the metabolic pathway.We introduce the “dominant rate constant” as a tool for deriving algebraic formulas relating rates of metabolic flux, sizes of metabolic pools, and the dynamics of isotopic enrichment. Illustrations of such algebraic formulas are provided for the rates of the citric acid cycle (CAC), glycolysis and glutamine synthesis in brain, as well as the rate of the CAC in heart. In addition, we prove that formulas for estimation of rates of glycolysis and of the CAC depend critically on the fractional turnover rates of lactate and glutamate, respectively.The justification for analysis of simulated data is that we are studying the effects of simplifications of metabolic models on the accuracy of estimation of metabolic pathways. Our use of the dominant rate constant is an analytical convenience that allows us to assess proposed simplifications of metabolic pathways. [Copyright &y& Elsevier]

Highlights: [•] The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. [•] Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. [•] There is an inverse relationship between expression of CDKN2B and adipogenic genes. [•] CDKN2B expression influences to postprandial triacylglycerol clearance. [•] CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. [Copyright &y& Elsevier]

Abstract: The SLC2A10 gene encodes a glucose transporter and is located on chromosome 20q13, where evidence has been found for linkage to type 2 diabetes (T2D) in multiple studies. We investigated SLC2A10 as a T2D candidate gene in Finns. We did not confirm the previously reported association between Ala206Thr and fasting insulin and we observed no statistically significant evidence for T2D association with any single marker. We tested haplotypes for association with diabetes-related traits and observed no excess of significant results. [Copyright &y& Elsevier]