Lactate overrides central nervous but not beta-cell glucose sensing in humans.
Lactate has been shown to serve as an alternative energy substrate in the central nervous system and to interact with hypothalamic glucose sensors. On the background of marked similarities between central nervous and beta-cell glucose sensing, we examined whether lactate also interacts with pancreatic glucose-sensing mechanisms in vivo. The effects of intravenously infused lactate vs placebo (saline) on central nervous and pancreatic glucose sensing were assessed during euglycemic and hypoglycemic clamp experiments in 10 healthy men. The release of neuroendocrine counterregulatory hormones during hypoglycemia was considered to reflect central nervous glucose sensing, whereas endogenous insulin secretion as assessed by serum C-peptide levels served as an indicator of pancreatic beta-cell glucose sensing. Lactate infusion blunted the counterregulatory hormonal responses to hypoglycemia, in particular, the release of epinephrine (P = .007) and growth hormone (P = .004), so that higher glucose infusion rates (P = .012) were required to maintain the target blood glucose levels. In contrast, the decrease in C-peptide concentrations during the hypoglycemic clamp remained completely unaffected by lactate (P = .60). During euglycemic clamp conditions, lactate infusion did not affect the concentrations of C-peptide and of counterregulatory hormones, with the exception of norepinephrine levels that were lower during lactate than saline infusion (P = .049) independently of the glycemic condition. Data indicate that glucose sensing of beta-cells is specific to glucose, whereas glucose sensing at the central nervous level can be overridden by lactate, reflecting the brain's ability to rely on lactate as an alternative major energy source.
Schmid
Sebastian M
SM
Department of Internal Medicine I, University of Luebeck, D-23538 Luebeck, Germany.
Jauch-Chara
Kamila
K
Hallschmid
Manfred
M
Oltmanns
Kerstin M
KM
Peters
Achim
A
Born
Jan
J
Schultes
Bernd
B
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D019344:Lactic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010919:Placebos; D055815:Young Adult
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D010919:Placebos; D019382:Human Growth Hormone; D019344:Lactic Acid; D005934:Glucagon; D005947:Glucose; D004837:Epinephrine