production (Figure 22-1a). In contrast, glucagon, secreted by the a-cells of
pancreatic islets when blood glucose levels are low, represses glucose utiliza-
tion and promotes endogenous glucose production (Figure 22-1b). A careful
balance between the actions of insulin and glucagon therefore help maintain
blood glucose levels within a normal range.
Insulin receptors are essentially expressed ubiquitously, in large part as a
result of the mitogenic actions of this peptide hormone. In terms of glucose
metabolism, the actions of insulin on the liver, adipose, and skeletal muscle will
be the focus of this discussion, although insulin-mediated changes in satiety and
blood flow undoubtedly play a role in whole body glucose homeostasis. On bind-
ing to its cell surface receptor, insulin elicits a complex cascade of cellular sig-
naling events that have not been elucidated fully to date. This in turn increases
glucose transport into the cell (skeletal muscle and adipose), promotes storage of
excess carbon from glucose as glycogen (skeletal muscle and liver) and triglyc-
eride (TAG; liver and adipose), increases glucose utilization as a fuel source
(skeletal muscle, liver, and adipose), and decreases endogenous glucose produc-
tion (liver) (see Figure 22-1a). These actions of insulin can be either acute (affect-
ing activity of preexisting proteins) or chronic (altering protein levels).
Skeletal muscle and adipose express two major isoforms of glucose trans-
ports, GLUT 1 and GLUT 4. GLUT 1, a ubiquitously expressed glucose
Figure 22-1a. The flow of glucose to tissues under conditions of elevated
blood glucose concentration. When [glucose]blood is high, the insulin:glucagon
ratio is high, leading to the uptake of glucose into the tissues. Abbreviation:
TAG = triacylglycerol
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