Lactate overrides central nervous but not β-cell glucose sensing in humans

Background: Lactate has been shown to serve as an alternative energy substrate in the central nervous system and to interact with hypothalamic glucose sensors. In light of marked similarities between central nervous and β-cell glucose sensing, we examined whether lactate also interacts with pancreatic glucose sensing mechanisms in vivo. Methods: We investigated the effects of intravenously infused lactate (vs. placebo) on central nervous and pancreatic glucose sensing by performing euglycemic and hypoglycemic clamp experiments in 10 healthy men. Central nervous glucose sensing was considered to be reflected by the release of neuroendocrine counterregulatory hormones while endogenous insulin secretion as assessed by C-peptide levels served as an indicator of pancreatic ß-cell glucose sensing. Results: As expected, lactate infusion blunted counterregulatory hormonal responses to hypoglycemia, in particular the release of epinephrine (P=0.007) and growth hormone (P=0.004). Therefore, higher glucose infusion rates (P =0.012) were required to maintain the target blood glucose levels during hypoglycemia. In contrast, the decrease in C-peptide concentrations during the hypoglycemic clamp remained completely unaffected by lactate infusion (P =0.60). During euglycemic clamp conditions, lactate infusion did neither affect circulating concentrations of C-peptide nor of counterregulatory hormones, except of norepinephrine levels which were lower during lactate than placebo (saline) infusion (P =0.049) independently of the glycemic condition. Conclusion: Data indicate that glucose sensing of β-cells is specific to glucose whereas glucose sensing at the central nervous level can be overridden by lactate, reflecting the brain's capability to rely on lactate as major energy source as well.