Differential effects of glucose and lactate on glucosensing neurons in the ventromedial hypothalamic nucleus

作者：Song Z; Routh VH^*

来源：Diabetes, 2005, 54(1): 15-22.

DOI：10.2337/diabetes.54.1.15

Glucose directly alters the action potential frequency of glucosensing neurons in the ventromedial hypothalamic nucleus (VMN). Glucose-excited neurons increase, and glucose-inhibited neurons decrease, their action potential frequency as glucose increases from 0.1 to 2.5 mmol/l. Glucose-excited neurons utilize the ATP-sensitive K+ channel (K-ATP channel) to sense glucose, whereas glucose opens a chloride channel in glucose-inhibited neurons. We tested the hypothesis that lactate, an alternate energy substrate, also regulates the action potential frequency of VMN glucose-excited and -inhibited but not nonglucosensing neurons. As expected, lactate reversed the inhibitory effects of decreased glucose on VMN glucose-excited neurons via closure of the K-ATP channel. Although increasing glucose from 2.5 to 5 mmol/l did not affect the activity of glucose-excited neurons, the addition of 0.5 mmol/l lactate or the K-ATP channel blocker tolbutamide increased their action potential frequency. In contrast to the glucose-excited neurons, lactate did not reverse the effects of decreased glucose on VMN glucose-inhibited neurons. In fact, it increased their action potential frequency in both low and 2.5 mmol/l glucose. This effect was mediated by both K-ATP and chloride channels. Non-glucosensing neurons were not affected by lactate. Thus, glucose and lactate have similar effects on VMN glucose-excited neurons, but they have opposing effects on VMN glucose-inhibited neurons.

• 出版日期2005-1