Author(s): Akhil Sundar
Mentor(s): Owen Chan
Institution U of U
It has been previously demonstrated that poorly controlled Type 1 Diabetes results in an increase in extracellular lactate concentrations in the ventromedial hypothalamus (VMH) of the brain that contributes to suppression of the counterregulatory responses to hypoglycemia (blood glucose levels below 70 mg/dL). The mechanisms underlying the increase in VMH lactate concentrations in diabetes are not entirely clear. The current study evaluates whether this lactate is derived from the periphery (i.e from lactate in the blood) or whether it is generated locally in the brain itself. To answer this question, we delivered a 50% glucose bolus (1g/kg) intravenously to conscious, freely moving male Sprague Dawley rats 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. The derived results show that the glucose bolus induced a swift and significant rise in glucose levels in the plasma (300% change from baseline), followed by a substantial increase in plasma lactate (150% change from baseline). In addition, glucose and lactate levels in the hypothalamus also increased considerably. However, in animals treated with OXA, the rise in hypothalamic lactate was significantly reduced (P = 0.018) in comparison to the animals treated with aECF (P< 0.05). In summary, our data suggests that an acute increase in blood glucose levels can trigger the local production of lactate in the VMH, which may contribute to the development of counterregulatory failure to hypoglycemia in diabetes.