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This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/E654    most recent 00365.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Jin, E. S. Articles by Malloy, C. R. Search for Related Content PubMed PubMed Citation Articles by Jin, E. S. Articles by Malloy, C. R.

Differing mechanisms of hepatic glucose overproduction in triiodothyronine-treated rats vs. Zucker diabetic fatty rats by NMR analysis of plasma glucose

¹The Mary Nell and Ralph B. Rogers Magnetic Resonance Center, Department of Radiology, University of Texas Southwestern Medical Center, Dallas; ²Department of Chemistry, University of Texas at Dallas, Richardson; and ³Veterans Affairs North Texas Health Care System, Dallas, Texas

Submitted 11 August 2004 ; accepted in final form 17 November 2004

The metabolic mechanism of hepatic glucose overproduction was investigated in 3,3'-5-triiodo-L-thyronine (T₃)-treated rats and Zucker diabetic fatty (ZDF) rats (fa/fa) after a 24-h fast. ²H₂O and [U-¹³C₃]propionate were administered intraperitoneally, and [3,4-¹³C₂]glucose was administered as a primed infusion for 90 min under ketamine-xylazine anesthesia. ¹³C NMR analysis of monoacetone glucose derived from plasma glucose indicated that hepatic glucose production was twofold higher in both T₃-treated rats and ZDF rats compared with controls, yet the sources of glucose overproduction differed significantly in the two models by ²H NMR analysis. In T₃-treated rats, the hepatic glycogen content and hence the contribution of glycogenolysis to glucose production was essentially zero; in this case, excess glucose production was due to a dramatic increase in gluconeogenesis from TCA cycle intermediates. ¹³C NMR analysis also revealed increased phosphoenolpyruvate carboxykinase flux (4x), increased pyruvate cycling flux (4x), and increased TCA flux (5x) in T₃-treated animals. ZDF rats had substantial glycogen stores after a 24-h fast, and consequently nearly 50% of plasma glucose originated from glycogenolysis; other fluxes related to the TCA cycle were not different from controls. The differing mechanisms of excess glucose production in these models were easily distinguished by integrated ²H and ¹³C NMR analysis of plasma glucose.

gluconeogenesis; glycogenolysis; type 2 diabetes; thyroid hormone; isotopes; nuclear magnetic resonance

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