1776-LB: Hyperglycemia Stimulates Local Lactate Production in the Hypothalamus

We previously demonstrated that poorly controlled type 1 diabetes leads to an increase in extracellular lactate concentrations in the ventromedial hypothalamus (VMH) that contributes to suppressing the counterregulatory hormone responses to hypoglycemia. The mechanisms underlying the increase in VMH lactate in diabetes are not clear. The current study evaluates whether this lactate is derived from the periphery or whether it is generated locally in the brain. To answer this question, we gave conscious, freely moving male Sprague-Dawley rats a 50% glucose bolus (1g/kg) intravenously and measured changes in interstitial glucose and lactate in the VMH using microdialysis while infusing either artificial extracellular fluid (aECF; N=13) or sodium oxamate (OXA; N = 11), a lactate dehydrogenase-A inhibitor, through microinjection needles that targeted the VMH. Our results show that the glucose bolus led to a rapid and dramatic rise in plasma glucose levels, followed by an increase in plasma lactate (300% and 150% change from baseline, respectively). In addition, glucose and lactate in the hypothalamus also increased significantly. However, in animals treated with OXA, the rise in hypothalamic lactate was significantly reduced (P-value = 0.018). In summary, our data suggest that elevated blood glucose in diabetes possibly triggers the local production of lactate in the brain, which may contribute to the development of counterregulatory failure to hypoglycemia.