Figure 22-1b. The flow of glucose to tissues under conditions of low blood
glucose concentration. When [glucose]blood is low, the insulin:glucagon ratio is
low, leading to glycogenolysis and gluconeogenesis in the liver. Abbreviation:
TAG = triacylglycerol
transporter, resides almost exclusively at the cell surface, where it facilitates a
constant “basal” rate of glucose uptake into the cell. In contrast, GLUT 4,
whose expression is limited to skeletal muscle, heart, and adipose, can be
found both at the cell surface and within specialized intracellular vesicles.
Redistribution of GLUT 4 from intracellular vesicles to the cell surface in
response to insulin results in increased rates of glucose transport, thereby facil-
itating insulin-stimulated glucose disposal. In contrast to skeletal muscle and
adipose, the liver expresses GLUT 2. This is a freely reversible glucose trans-
porter that resides permanently at the cell surface. GLUT 2 enables glucose to
pass down its concentration gradient, allowing increased hepatic glucose
uptake when blood glucose levels are high and increased hepatic glucose
efflux when blood glucose levels are low.
Once within the cell, glucose undergoes one of several fates. Insulin pro-
motes incorporation of glucose moieties into glycogen, the storage form of glu-
cose in mammals. This is driven in large part by insulin-mediated activation of
protein phosphatase 1 (PP1; Figure 22-2a). PP1 dephosphorylates (hydrolytic
removal of regulatory phosphate groups from serine/threonine residues on
target enzymes) a number of key proteins involved in glycogen metabolism.
Dephosphorylation and activation of glycogen synthase (GS), with a con-
comitant dephosphorylation and inactivation of glycogen phosphorylase (GP),