In vivo metabolic response of glucose to dichloroacetate in humans

Jeff A. Brown, Dennis Gore

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Hyperglycemia is common in severely ill patients and is related principally to an increase in glucose production. Dichloroacetate (DCA), which is known to increase the rate of pyruvate oxidation, has been shown to lower plasma glucose concentrations in normal fasting subjects and in diabetics and thus may be efficacious in treating stress induced hyperglycemia. However, the mechanism by which DCA lowers the plasma glucose concentration in humans has not been elucidated. To examine the human in vivo metabolic alterations induced by DCA, six fasting volunteers were infused with 6,6-D2-glucose and indirect calorimetry was performed prior to and following DCA administration. Glucose, lactate, and alanine net balance across the leg were also quantitated. Following DCA administration, plasma glucose concentrations decreased by 9% due to a proportional decrease in the rate of glucose production (P < 0.05). DCA had no affect on glucose clearance or leg net balance; however, the rate of glucose oxidation increased by 24% from baseline (P < 0.05). This increase in glucose oxidation without a compensatory change in peripheral glucose consumption suggests an improved efficiency in peripheral glucose utilization induced by DCA. Plasma concentrations of lactate and alanine were also lowered by DCA (56% for lactate, 66% for alanine, P < 0.05) without a significant alteration in leg net balance. These results suggest that DCA may decrease gluconeogenesis by limiting the availability of the precursor substrates lactate and alanine. Thus dichloroacetate may be an appropriate alternative to insulin in correcting mild elevations in plasma glucose concentrations. Furthermore, DCA may be especially effective in severely ill patients where hyperglycemia is largely due to increases in gluconeogenesis.

Original languageEnglish (US)
Pages (from-to)391-394
Number of pages4
JournalJournal of Surgical Research
Volume61
Issue number2
DOIs
StatePublished - Mar 1996
Externally publishedYes

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Glucose
Alanine
Lactic Acid
Hyperglycemia
Leg
Gluconeogenesis
Fasting
Indirect Calorimetry
Pyruvic Acid
Volunteers
Insulin

ASJC Scopus subject areas

  • Surgery

Cite this

In vivo metabolic response of glucose to dichloroacetate in humans. / Brown, Jeff A.; Gore, Dennis.

In: Journal of Surgical Research, Vol. 61, No. 2, 03.1996, p. 391-394.

Research output: Contribution to journalArticle

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