Glucose Sensing Neurons in the Ventromedial Hypothalamus

Vanessa H Routh

doi:10.3390/s101009002

Abstract

Neurons whose activity is regulated by glucose are found in a number of brain regions. Glucose-excited (GE) neurons increase while glucose-inhibited (GI) neurons decrease their action potential frequency as interstitial brain glucose levels increase. We hypothesize that these neurons evolved to sense and respond to severe energy deficit (e.g., fasting) that threatens the brains glucose supply. During modern times, they are also important for the restoration of blood glucose levels following insulin-induced hypoglycemia. Our data suggest that impaired glucose sensing by hypothalamic glucose sensing neurons may contribute to the syndrome known as hypoglycemia-associated autonomic failure in which the mechanisms which restore euglycemia following hypoglycemia become impaired. On the other hand, increased responses of glucose sensing neurons to glucose deficit may play a role in the development of Type 2 Diabetes Mellitus and obesity. This review will discuss the mechanisms by which glucose sensing neurons sense changes in interstitial glucose and explore the roles of these specialized glucose sensors in glucose and energy homeostasis.

Highlights

It is clear that the brain regulates energy homeostasis
This suggests that the neuropeptide Y (NPY)-GI neurons may belong to the population of NPY neurons which project to the PVH and play a role in food intake [112]. nNOS-KO mice that lack GI neurons in the mediobasal hypothalamus (ARC + VMN) showed significantly decreased epinephrine responses to hypoglycemia suggesting that VMN GI neurons are involved in the sympathoadrenal cCRR [100]
ventromedial hypothalamus (VMH) glucose sensing neurons serve to protect the brain during times of severe glucose deficit

Summary

Introduction

It is clear that the brain regulates energy homeostasis. The brain responds to circulating signals of nutrient status and adjusts food intake [1]. Interstitial brain glucose levels below 0.7 mM and above 2.5 mM are associated with pathological hypo- and hyperglycemia, respectively [11] Both VMH GE and GI neurons are extremely sensitive to glucose changes under 2 mM, with minimal response above 2 mM suggesting that these glucose sensing neurons primarily sense glucose deficit [30,31]. It would not be energetically efficient if small meal to meal changes in glucose levels altered the systems responsible for protecting the brain against the dangers of hypoglycemia This hypothesis further posits that during normal energy homeostasis it would be important that these glucose sensing neurons do not respond to small glucose decreases associated with meal to meal fluctuations in blood glucose and activate the powerful homeostatic systems present in the VMH. The data will be summarized and interpreted with regard to the proposed hypotheses

GE Neurons

GI Neurons

Fasting

Glucose Sensing Neurons and T2DM

Findings

Summary