Recurrent Glucose Deprivation Leads to the Preferential Use of Lactate by Neurons in the Ventromedial Hypothalamus.

Recurrent Glucose Deprivation Leads to the Preferential Use of Lactate by Neurons in the Ventromedial Hypothalamus. Am J Physiol Endocrinol Metab. 2019 Mar 19;: Authors: Shah M, Addison A, Wang P, Zhu W, Chan O Abstract Increased GABAergic output in the ventromedial hypothalamus (VMH) contributes to counterregulatory failure in recurrently hypoglycemic (RH) rats and lactate, an alternate fuel source in the brain, contributes to this phenomenon. The current study assessed whether recurring bouts of glucose deprivation enhanced neuronal lactate uptake and if so, whether this influenced GABA output and the counterregulatory responses. Glucose deprivation was induced using 5-thioglucose (5TG). Control rats received an infusion of artificial extracellular fluid. These groups were compared to RH animals. On day 4, the rats underwent a hypoglycemic clamp with microdialysis. To test whether 5TG affected neuronal lactate utilization, a subgroup of 5TG-treated rats was microinjected with the lactate transporter inhibitor (4CIN) just prior to the start of the clamp. Both RH and 5TG raised VMH GABA levels and this was associated with impaired counterregulatory responses. 4CIN reduced VMH GABA levels and restored the hormone responses in the 5TG group. We then evaluated 14C-lactate uptake in hypothalamic neuronal cultures. Recurring exposure to low glucose increased MCT2 mRNA expression and augmented lactate uptake. Taken together, our data sugge...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research