Glucose is an important signal that regulates glucose and energy
homeostasis but its precise physiological role and signaling mechanism
in the brain are still uncompletely understood. Over the recent
years we have investigated the possibility that central glucose sensing
may share functional similarities with glucose sensing by pancreatic
beta-cells, in particular a requirement for the expression of
the glucose transporter Glut2. Using mice with genetic inactivation
of Glut2, but rescued pancreatic beta-cell function by transgenic
expression of a glucose transporter, we have established that extrapancreatic
glucose sensors are involved: i) in the control of glucagon
secretion in response to hypoglycemia, ii) in the control of feeding
and iii) of energy expenditure. We have more recently shown that
central Glut2-dependent glucose sensors are involved in the regulation
of NPY and POMC expression by arcuate nucleus neurons
and that the sensitivity to leptin of these neurons is enhanced by
Glut2-dependent glucose sensors. Using mice with genetic tagging
of Glut2-expressing cells, we determined that the NPY and POMC
neurons did not express Glut2 but were connected to Glut2 expressing
neurons located most probably outside of the arcuate nucleus.
We are now defining the electrophysiological behavior of these
Glut2 expressing neurons. Our data provide an initial map of glucose
sensing neurons expressing Glut2 and link these neurons with
the control of specific physiological function.