section 22.5
Carbohydrate Homeostasis
499
5. The liver plays a major role in converting excess
glucose into triacylglycerols, packaging them into
VLDLs, and exporting them to nonhepatic tissues.
Thus, glucose in excess of that needed to restore
glycogen levels ends up stored as triacylglycerol in
adipocytes.
6
. Glucose that is not sequestered in the liver is
eventually distributed within the extracellular space
and accounts for the increased plasma glucose levels.
This glucose is rapidly metabolized by the other
tissues.
7. Insulin stimulates uptake of glucose into muscle by
recruiting more glucose transporters to the cell
membrane. The glucose that is taken up will be used
to replenish muscle stores of glycogen through
reaction mechanisms similar to those depicted in
Figure 22-10 (except that glucagon does not regulate
muscle metabolism). Muscle glycogen levels will be
restored, while any protein degraded for
gluconeogenesis during fasting will be replenished.
The signal for increased protein synthesis is insulin.
8
. Much of the glucose not taken up by liver and muscle
is taken up by adipocytes under the influence of
insulin-stimulated transport of glucose into the cell.
Esterification of fatty acids for storage as
triacylglycerols is dependent on the availability of
«-glycerophosphate derived
in situ
from glucose. The
glucose can also be converted into fatty acids from
acetyl-CoA generated via glycolysis and the pyruvate
dehydrogenase reaction and from NADPH obtained
via the pentose phosphate pathway.
9. With the exception of brain, liver, and blood cells,
insulin directly stimulates the entrance of glucose that
is used for anabolic processes in most cells of the
body.
The disposition of a high glucose intake is presented in
Figure 22-11.
As much glucose as possible is stored in liver and mus-
cle, and the remainder is used for biosynthetic purposes
or converted to fatty acids and stored as triacylglycerol.
Fatty acid synthesis in liver leads to secretion of tria-
cylglycerols as VLDLs and transport to adipose tissue.
Plasma glucose levels do not exceed the renal threshold
of 200 mg/dL for glucose. Insulin stimulates a variety
of anabolic processes in addition to those of glycogen,
protein, and triacylglycerol synthesis by mechanisms that
may involve rapid, covalent modification of key regulatory
enzymes or regulation of their synthesis. Insulin stimu-
lates glycolysis for provision of anabolic metabolites. Low
levels of glucagon, glucocorticoids, and catecholamines,
which oppose the action of insulin, also contribute to rapid
removal of glucose.
Glucose Tolerance
Intake of carbohydrate leads to a characteristic change
in blood glucose level that may be affected by many fac-
tors, such as abnormalities in insulin secretion or effective-
ness. Normal and abnormal glucose tolerance responses
are shown in Ligure 22-12. The test is performed on a
patient who has fasted overnight and is at rest. The pa-
tient ingests 75 g of glucose, and the blood glucose level
is measured over a 2- to 4-hour period. In a normal in-
dividual, the fasting level is constant before and shortly
after glucose ingestion. Only values outside the range of
normal fasting values (denoted by the shaded bar) are
helpful diagnostically. Glucose intolerance is manifested
by a slower return to the fasting level. Many factors af-
fect the shape of the curve. After an overnight fast, hep-
atic glycogen stores will be low, but if the fast is shorter
they may be much higher and the plasma glucose lev-
els would remain elevated longer. Tissue sensitivity to
insulin is modulated by past dietary composition, obe-
sity, stress, age, and exercise. After a diet rich in carbo-
hydrate, for example, insulin levels would be increased
by down-regulation of insulin receptors, tissue insulin in-
sensitivity, and glucose intolerance. After fasting or on
a low-carbohydrate diet, insulin responsiveness and glu-
cose tolerance would be greater. Exercise enhances in-
sulin sensitivity. The pattern shown in Ligure 22-12 is
typical of glucose intolerance observed at the onset of
insulin-independent diabetes. The fasting level of glucose
is frequently in the normal range in mild diabetes, but after
glucose ingestion the level stays higher for a longer period
of time.
As the plasma glucose level decreases, it falls slightly
below the fasting level before returning to normal, since
restoration of insulin to the normal fasting level occurs
slightly after that of the blood glucose level. This de-
pression can be heightened in “reactive hypoglycemia.”
If, after a fast of 18-24 hours a small amount of glu-
cose in a highly digestible form is consumed (such as
the sucrose in a candy bar), the blood glucose level
will be temporarily elevated followed by rapid eleva-
tion of insulin level, rapid entry of glucose into tis-
sues, and depression of plasma glucose level below
normal.
Glucose Homeostasis during Fasting
During most of the day the plasma glucose level remains
constant, even after a 24-hour fast. In very prolonged fasts,
the plasma glucose level decreases very slightly. During
these periods, glucose is being actively metabolized by tis-
sues such as brain and red blood cells, and is replenished.
During a 24-hour fast, the body uses approximately 180 g
