title: Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.
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.
authors.affiliation: 1University of California, Los Angeles, Cerebral Blood Flow Laboratory, Los Angeles, California.|2Division of Neurosurgery, University of California, Los Angeles (UCLA), UCLA Center for Health Sciences, Los Angeles, California.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Glenn
authors.affiliation: 1University of California, Los Angeles, Cerebral Blood Flow Laboratory, Los Angeles, California.|2Division of Neurosurgery, University of California, Los Angeles (UCLA), UCLA Center for Health Sciences, Los Angeles, California.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Martin
authors.affiliation: 1University of California, Los Angeles, Cerebral Blood Flow Laboratory, Los Angeles, California.
authors.forename: David L
authors.initials: DL
authors.lastname: McArthur
authors.affiliation: 1University of California, Los Angeles, Cerebral Blood Flow Laboratory, Los Angeles, California.
authors.forename: David A
authors.initials: DA
authors.lastname: Hovda
authors.affiliation: 1University of California, Los Angeles, Cerebral Blood Flow Laboratory, Los Angeles, California.
authors.forename: Paul
authors.initials: P
authors.lastname: Vespa
authors.affiliation: 3Department of Integrative Biology, University of California, Berkeley, Berkeley, California.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Johnson
authors.affiliation: 3Department of Integrative Biology, University of California, Berkeley, Berkeley, California.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Horning
authors.affiliation: 3Department of Integrative Biology, University of California, Berkeley, Berkeley, California.
authors.forename: George A
authors.initials: GA
authors.lastname: Brooks
mesh_terms: D000293:Adolescent; D000328:Adult; D001930:Brain Injuries / Q000097:blood* / Q000175:diagnosis; D005260:Female; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status / Q000502:physiology*; D055815:Young Adult
chemical_list: D019344:Lactic Acid; D005947:Glucose
keywords: TBI; brain; gluconeogenesis; glucose; glucose homeostasis; glycemia; lactate; mass spectrometry