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J Neurotrauma. 2015 Jun 1;32(11):811-9. doi: 10.1089/neu.2014.3482. Epub 2015 Mar 11.

Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

Author information

1
1University of California, Los Angeles, Cerebral Blood Flow Laboratory, Los Angeles, California.
2
2Division of Neurosurgery, University of California, Los Angeles (UCLA), UCLA Center for Health Sciences, Los Angeles, California.
3
3Department of Integrative Biology, University of California, Berkeley, Berkeley, California.

Abstract

We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-(2)H2]glucose, i.e., D2-glucose, and [3-(13)C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2-10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain.

KEYWORDS:

TBI; brain; gluconeogenesis; glucose; glucose homeostasis; glycemia; lactate; mass spectrometry

PMID:
25279664
PMCID:
PMC4530391
DOI:
10.1089/neu.2014.3482
[Indexed for MEDLINE]
Free PMC Article

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