Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor ...

Clinical and experimental studies have revealed that altered glucose status is an
important factor controlling learning and memory processes (Messier & Gagnon,
1996). Although under basal conditions the rate of glucose transport is not the
rate-limiting step for glycolysis in the central nervous system hypoglycemia or
hyperglycemia is known to change the glucose transport system in the brain
(Devivo, et al., 1991) suggesting that there should be glucose-regulatable
mechanisms associated with the transport of glucose. The brain is dependent on a
steady supply of glucose (Erecinska & Silver, 1994).
Neuronal glucose uptake relies on the glucose transporter isoforms
GLUT1 (Maher et al., 1994), GLUT3 (Olson & Pessin, 1996), and GLUT8 (Piroli
et al., 2002; Sankar et al., 2002) on the plasma membrane. Due to its relative
abundance in the brain, GLUT3 is often considered the neuronal glucose
transporter (Maher et al., 1994). GLUT3 is a major facultative glucose transporter
expressed in neurons, though there is evidence for expression in neurons of
GLUT1, GLUT2, GLUT4, GLUT5 and GLUT8 (Choeiri et al., 2002). Classically,
neurons are considered to be insulin insensitive, that is, glucose uptake is not
significantly increased in response to insulin stimulation (Heidenreich et al., 1989)
as is regularly observed in muscle and fat cells (Watson & Pessin, 2001). Insulin
treatment dramatically increased the translocation of GLUT 3 to the plasma
membrane, and insulin pre-treatment potentiated a KCl stimulated glucose uptake
(Uemura & Greenlee, 2006).
Although neurons have insulin receptors (Schulingkamp et al., 2000), they
do not respond to insulin alone by increasing glucose uptake. In insulin-sensitive
cells, insulin increases glucose uptake by promoting two critical processes:
translocation of vesicles containing the glucose transporter isoform GLUT4 to the
plasma membrane and their fusion with the plasma membrane (Czech & Corvera,
1999; Olson & Pessin, 1996. In neurons, fusion of GLUT3 with the plasma
membrane is induced by membrane depolarization, resulting in a marked increase
in glucose uptake (Uemura & Greenlee, 2001). It is well known that nerve cells in
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