TY - JOUR
T1 - Lactate-Protected Hypoglycemia (LPH)
AU - Goodwin, Matthew L.
AU - Gladden, L. Bruce
AU - Nijsten, Maarten W.N.
N1 - Publisher Copyright:
© Copyright © 2020 Goodwin, Gladden and Nijsten.
PY - 2020/9/3
Y1 - 2020/9/3
N2 - Here, we provide an overview of the concept of a lactate-protected hypoglycemia (“LPH”), originally proposed as lowering glucose while simultaneously increasing lactate concentration as a method by which tumors might be targeted. Central to this hypothesis is that lactate can act as a critical salvage fuel for the central nervous system, allowing for wide perturbations in whole body and central nervous system glucose concentrations. Further, many tumors exhibit “the Warburg” effect, consuming glucose and producing and exporting lactate despite adequate oxygenation. While some recent data have provided evidence for a “reverse-Warburg,” where some tumors may preferentially consume lactate, many of these experimental methods rely on a significant elevation in lactate in the tumor microenvironment. To date it remains unclear how various tumors behave in vivo, and how they might respond to perturbations in lactate and glucose concentrations or transport inhibition. By exploiting and targeting lactate transport and metabolism in tumors (with a combination of changes in lactate and glucose concentrations, transport inhibitors, etc.), we can begin developing novel methods for targeting otherwise difficult to treat pathologies in the brain and spinal cord. Here we discuss evidence both experimental and observational, and provide direction for next steps in developing therapies based on these concepts.
AB - Here, we provide an overview of the concept of a lactate-protected hypoglycemia (“LPH”), originally proposed as lowering glucose while simultaneously increasing lactate concentration as a method by which tumors might be targeted. Central to this hypothesis is that lactate can act as a critical salvage fuel for the central nervous system, allowing for wide perturbations in whole body and central nervous system glucose concentrations. Further, many tumors exhibit “the Warburg” effect, consuming glucose and producing and exporting lactate despite adequate oxygenation. While some recent data have provided evidence for a “reverse-Warburg,” where some tumors may preferentially consume lactate, many of these experimental methods rely on a significant elevation in lactate in the tumor microenvironment. To date it remains unclear how various tumors behave in vivo, and how they might respond to perturbations in lactate and glucose concentrations or transport inhibition. By exploiting and targeting lactate transport and metabolism in tumors (with a combination of changes in lactate and glucose concentrations, transport inhibitors, etc.), we can begin developing novel methods for targeting otherwise difficult to treat pathologies in the brain and spinal cord. Here we discuss evidence both experimental and observational, and provide direction for next steps in developing therapies based on these concepts.
KW - hyperlactatemia
KW - hypoglycemia
KW - lactate
KW - lactate dehydrogenase
KW - monocarboxylate transporter
KW - shuttle
UR - http://www.scopus.com/inward/record.url?scp=85091299382&partnerID=8YFLogxK
U2 - 10.3389/fnins.2020.00920
DO - 10.3389/fnins.2020.00920
M3 - Article
C2 - 33013305
AN - SCOPUS:85091299382
SN - 1662-4548
VL - 14
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
M1 - 920
ER -