582
Chapter 16
Uptake of the HDL by the liver and these endocrine cells is
facilitated by the presence in their plasma membranes of large
numbers of receptors specifi c for HDL, which bind to the
receptors and then are taken into the cells.
LDL cholesterol is often designated “bad” cholesterol
because high plasma levels are associated with increased
deposition of cholesterol in arterial walls and a higher
incidence of heart attacks. (The designation “bad” should
not obscure the fact that LDL is essential for supplying cells
with the cholesterol they require to synthesize cell membranes
and, in the case of the gonads and adrenal glands, steroid
hormones.) Using the same criteria, HDL cholesterol has
been designated “good” cholesterol.
The best single indicator of the likelihood of developing
atherosclerotic heart disease is, therefore, not total plasma
cholesterol but rather the ratio of plasma LDL cholesterol to
plasma HDL cholesterol—the lower the ratio, the lower the
risk. Cigarette smoking, a known risk factor for heart attacks,
lowers plasma HDL, whereas weight reduction (in overweight
persons) and regular exercise usually increase it. Estrogen not
only lowers LDL but raises HDL, which explains, in part, why
premenopausal women have less coronary artery disease than
men. After menopause, the cholesterol values and coronary
artery disease rates in women not on hormone replacement
therapy (Chapter 17) become similar to those in men.
Finally, a great variety of cholesterol metabolism
disorders have been identifi ed in the human population. In
familial hypercholesterolemia
,
for example, LDL receptors
are reduced in number or are nonfunctional. Consequently,
LDL accumulates in the blood to very high levels. If
untreated, this disease may result in atherosclerosis and heart
disease at unusually young ages.
SECTION A SUMMARY
Events of the Absorptive and Postabsorptive States
I. During absorption, energy is provided primarily by absorbed
carbohydrate. Net synthesis of glycogen, triglyceride, and
protein occurs.
a. Some absorbed carbohydrate not used for energy is
converted to glycogen, mainly in the liver and skeletal
muscle, but most is converted, in liver and adipocytes, to
α
-glycerol phosphate and fatty acids, which then combine
to form triglycerides. The liver releases its triglycerides in
very-low-density lipoproteins, the fatty acids of which are
picked up by adipocytes.
b. The fatty acids of some absorbed triglycerides are used for
energy, but most are rebuilt into fat in adipose tissue.
c. Some absorbed amino acids are converted to proteins, but
excess amino acids are converted to carbohydrate and fat.
d. There is a net upake of glucose by the liver.
II. In the postabsorptive state, blood glucose level is maintained
by a combination of glucose production by the liver and
a switch from glucose utilization to fatty acid and ketone
utilization by most tissues.
a. Synthesis of glycogen, fat, and protein is curtailed, and net
breakdown of these molecules occurs.
b. The liver forms glucose by glycogenolysis of its own glycogen
and by gluconeogenesis from lactate and pyruvate (from the
breakdown of muscle glycogen), glycerol (from adipose tissue
lipolysis), and amino acids (from protein catabolism).
c. Glycolysis is decreased, and most of the body’s energy
supply comes from the oxidation of fatty acids released by
adipose tissue lipolysis and of ketones produced from fatty
acids by the liver.
d. The brain continues to use glucose but also starts using
ketones as they build up in the blood.
Endocrine and Neural Control of the Absorptive
and Postabsorptive States
I. The major hormones secreted by the pancreatic islets of
Langerhans are insulin by the beta cells and glucagon by the
alpha cells.
II. Insulin is the most important hormone controlling metabolism.
a. In muscle, it stimulates glucose uptake, glycolysis,
and net synthesis of glycogen and protein. In adipose
tissue, it stimulates glucose uptake and net synthesis
of triglyceride. In liver, it inhibits gluconeogenesis
and glucose release and stimulates the net synthesis of
glycogen and triglycerides.
b. The major stimulus for insulin secretion is an increased
plasma glucose concentration, but secretion is also infl uenced
by many other factors summarized in Figure 16–8.
III. Glucagon, epinephrine, cortisol, and growth hormone all exert
effects on carbohydrate and lipid metabolism that are opposite,
in one way or another, to those of insulin. They raise plasma
concentrations of glucose, glycerol, and fatty acids.
a. Glucagon’s physiological actions are on the liver, where
it stimulates glycogenolysis, gluconeogenesis, and ketone
synthesis.
b. The major stimulus for glucagon secretion is hypoglycemia,
but secretion is also stimulated by other inputs, including
the sympathetic nerves to the islets.
c. Epinephrine released from the adrenal medulla in response
to hypoglycemia stimulates glycogenolysis in the liver
and muscle, gluconeogenesis in the liver, and lipolysis in
adipocytes. The sympathetic nerves to liver and adipose
tissue exert effects similar to those of epinephrine.
d. Cortisol is permissive for gluconeogenesis and lipolysis;
in higher concentrations, it stimulates gluconeogenesis
and blocks glucose uptake. These last two effects are also
exerted by growth hormone.
Energy Homeostasis in Exercise and Stress
I. During exercise, the muscles use as their energy sources plasma
glucose, plasma fatty acids, and their own glycogen.
a. Glucose is provided by the liver, and fatty acids are provided
by adipose tissue lipolysis.
b. The changes in plasma insulin, glucagon, and epinephrine are
similar to those that occur during the postabsorptive period
and are mediated mainly by the sympathetic nervous system.
II. Stress causes hormonal changes similar to those caused by
exercise.
Additional Clinical Examples
I. T1DM is due to insulin defi ciency and can lead to diabetic
ketoacidosis if untreated.
II. T2DM is usually associated with obesity and is caused by a
combination of insulin resistance and a defect in beta cell
responsiveness to elevated plasma glucose concentration.
Plasma insulin concentration is usually normal or elevated.
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