Presentation description

Iatrogenic hypoglycemia remains a barrier for people with type 1 diabetes (T1D) trying to achieve good glucose control. Hypoglycemia triggers a "counterregulatory hormone response", including an increase of glucagon and epinephrine, that help restore glucose levels to normal. However, people with poorly controlled T1D lose the ability to secrete glucagon and have an impaired epinephrine response that increases their risk for experiencing hypoglycemia. The mechanisms underlying this defect are unknown but may be linked to a rise in lactate levels within the ventromedial hypothalamus (VMH), a key glucose sensing region in the brain, that prevents it from detecting falling glucose levels and eliciting appropriate responses. The aim of this study was to investigate whether acute increases in blood glucose raise lactate levels within the VMH. To address this question, we bolused glucose systemically into non-diabetic rats and monitored for glucose and lactate changes in both the blood and the VMH in the presence (n=5) or absence of oxamate (n=6), which inhibits lactate production. Interestingly, both brain glucose and lactate rose simultaneously 15 minutes after the glucose bolus. However, the rise in VMH lactate was prevented when oxamate was injected into the VMH (P<0.05). The data suggests a rise in peripheral glucose triggers local lactate production in the VMH and that the rise may not come from peripheral sources. Further, hyperglycemia may play a role in stimulating lactate production in the VMH that suppresses the counterregulatory responses in poorly controlled T1D.