Amygdala Glucose-Sensing Neurons Regulate Glucose Metabolism

Dysfunction of blood glucose produces health problems with profound consequences. In humans, the central nervous system (CNS) plays a vital role in glucose metabolism. The medial and basomedial amygdalar nuclei contain neurons that alter their firing in response to physiological changes in glucose concentrations and express glucokinase (GK), an enzyme thought to act as a glucose sensor in the CNS. However, little is known about the anatomy and function of these neurons. We have found that amygdala neurons express cfos, a marker of neuronal activation, in response to changes in blood glucose. Using a transgenic mouse with Cre recombinase expression in GK neurons and the retrograde tracer pseudorabies virus (PRV), we have also found that GK-expressing neurons in the amygdala are part of a polysynaptic circuit to peripheral endocrine organs. Finally, modulating the activity of amygdala neurons alters both feeding and glucose metabolism. Together, these data support a role for amygdala glucose-sensing neurons in the regulation of glucose metabolism and behaviors that restore circulating glucose levels to normal.