Regulation of Organic Metabolism and Energy Balance
As noted earlier,
is the peptide hormone produced
by the alpha cells of the pancreatic islets. The major physiologi-
cal effects of glucagon occur within the liver and oppose those
of insulin (
Figure 16–9
). Thus, glucagon (1) increases glyco-
gen breakdown, (2) increases gluconeogenesis, and (3) increases
the synthesis of ketones. The overall results are to increase
the plasma concentrations of glucose and ketones, which are
important for the postabsorptive period, and to prevent hypo-
glycemia. The effects, if any, of glucagon on adipocyte func-
tion in humans are still unresolved.
From a knowledge of these effects, you might predict
that glucagon secretion should increase during the postab-
sorptive period and periods of prolonged fasting; this is indeed
the case. The major stimulus for glucagon secretion at these
times is hypoglycemia. The adaptive value of such a refl ex is
clear: A decreasing plasma glucose concentration induces an
increase in the secretion of glucagon into the blood, which,
by its effects on metabolism, serves to restore normal blood
glucose concentration by glycogenolysis and gluconeogenesis.
At the same time, glucagon supplies ketones for utilization by
the brain. Conversely, an increased plasma glucose concentra-
tion inhibits glucagon’s secretion, thereby helping to return
the plasma glucose concentration toward normal. Thus, dur-
ing the postabsorptive state, plasma insulin concentration is
and plasma glucagon concentration is
and this com-
bined change accounts almost entirely for the transition from
the absorptive to the postabsorptive state. Said in a different
way, this shift is best explained by a rise in the glucagon: insu-
lin ratio in the plasma.
The secretion of glucagon, like that of insulin, is con-
trolled not only by the plasma concentration of glucose and
other nutrients but also by neural and hormonal inputs to the
islets. For example, the sympathetic nerves to the islets stimu-
late glucagon secretion—just the opposite of their effect on
insulin secretion.
Epinephrine and Sympathetic Nerves to Liver
and Adipose Tissue
As noted earlier, epinephrine and the sympathetic nerves to
the pancreatic islets inhibit insulin secretion and stimulate glu-
cagon secretion. In addition, epinephrine also affects nutrient
metabolism directly (
Figure 16–10
). Its major direct effects
include stimulation of (1) glycogenolysis in both the liver and
skeletal muscle, (2) gluconeogenesis in the liver, and (3) lipol-
ysis in adipocytes. Activation of the sympathetic nerves to the
liver and adipose tissue elicits essentially the same responses
from these organs as does circulating epinephrine.
In adipocytes, epinephrine stimulates the activity of
an enzyme called
hormone-sensitive lipase (HSL).
activated, HSL causes the breakdown of triglycerides to free
fatty acids and glycerol. Both are then released into the blood,
where they serve directly as a fuel source (fatty acids) or as a
gluconeogenic precursor (glycerol). Not surprisingly, insulin
inhibits the activity of HSL during the absorptive state.
Thus, enhanced sympathetic nervous system activity
exerts effects on organic metabolism—specifi cally, increased
plasma concentrations of glucose, glycerol, and fatty acids—
that are opposite those of insulin.
As might be predicted from these effects, hypoglyce-
mia leads to increases in both epinephrine secretion and sym-
pathetic nerve activity to the liver and adipose tissue. This is
the same stimulus that leads to increased glucagon secretion,
although the receptors and pathways are totally different.
When the plasma glucose concentration decreases, glucose
receptors in the central nervous system (and, possibly, the liver)
initiate the refl exes that lead to increased activity in the sympa-
thetic pathways to the adrenal medulla, liver, and adipose tis-
sue. The adaptive value of the response is the same as that for
Plasma amino
insulinotropic peptide
Plasma epinephrine
Pancreatic islet beta cells
Insulin secretion
Figure 16–8
Major controls of insulin secretion. The
represent stimulatory and inhibitory actions, respectively. GIP is a
gastrointestinal hormone that acts as a feedforward signal to the
Plasma glucose
Plasma ketones
Pancreatic islet alpha cells
Glucagon secretion
Plasma glucose
Ketone synthesis
Plasma glucagon
Figure 16–9
Nature of plasma glucose control over glucagon secretion.
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