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

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Abstract

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 T 3-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 T 3-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume288
Issue number4 51-4
DOIs
StatePublished - Apr 2005

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Triiodothyronine
Rats
Nuclear magnetic resonance
Plasmas
Glucose
Liver
Fluxes
Zucker Rats
Glycogenolysis
Thyronines
Xylazine
Liver Glycogen
Phosphoenolpyruvate
Gluconeogenesis
Propionates
Ketamine
Pyruvic Acid
Glycogen
Animals
Anesthesia

Keywords

  • Gluconeogenesis
  • Glycogenolysis
  • Isotopes
  • Nuclear magnetic resonance
  • Thyroid hormone
  • Type 2 diabetes

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

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title = "Differing mechanisms of hepatic glucose overproduction in triiodothyronine-treated rats vs. Zucker diabetic fatty rats by NMR analysis of plasma glucose",
abstract = "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 T 3-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 T 3-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.",
keywords = "Gluconeogenesis, Glycogenolysis, Isotopes, Nuclear magnetic resonance, Thyroid hormone, Type 2 diabetes",
author = "Jin, {Eunsook S.} and Burgess, {Shawn C.} and Merritt, {Matthew E.} and Sherry, {A. Dean} and Malloy, {Craig R.}",
year = "2005",
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language = "English (US)",
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journal = "American Journal of Physiology - Heart and Circulatory Physiology",
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T1 - Differing mechanisms of hepatic glucose overproduction in triiodothyronine-treated rats vs. Zucker diabetic fatty rats by NMR analysis of plasma glucose

AU - Jin, Eunsook S.

AU - Burgess, Shawn C.

AU - Merritt, Matthew E.

AU - Sherry, A. Dean

AU - Malloy, Craig R.

PY - 2005/4

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N2 - 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 T 3-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 T 3-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.

AB - 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 T 3-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 T 3-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.

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