section 22.5
Carbohydrate Homeostasis
497
low level, increases to a maximum by about the fourth, and
then decreases to a point below the initial level. Protein is
not mobilized rapidly and even at maximum utilization
accounts for only ~25% of fuel expenditure.
Protein degradation is limited mainly to the mainte-
nance of blood glucose. Starting postprandially, oxida-
tion of lipid accounts for the bulk of fuel utilization for
metabolic homeostasis. As fasting progresses, the total
energy utilized slowly decreases, reflecting the decreasing
energy expenditure, but lipid continues to be the major en-
ergy source. Few people in developed countries undergo
direct prolonged starvation, but disorders such as alco-
holism and anorexia nervosa reflect a similar pattern of
fuel utilization. The starvation pattern is very helpful for
understanding metabolic control and will be used through-
out this chapter. The metabolic controls that function in a
long-term fast are similar to those that occur in the normal
day-to-day pattern of fasting and feeding.
Appetite, Hunger, and Control of Food Intake
The perception that the extent of food intake by humans
is poorly controlled is false because most people, once
they have matured physiologically, maintain a stable body
weight. There appears to be a set point for weight (as there
is for body temperature) in each individual. During fasting,
body weight decreases. Upon refeeding, an initially greater
intake of food returns the body to the original weight. Con-
versely, if a mammal is force-fed body weight increases,
but when force-feeding is stopped, the animal voluntarily
decreases food intake until the body has returned to the
original weight. Even in most cases of obesity, a set body
weight is manifest, albeit at a higher than normal level.
A 70-kg adult typically consumes 5-10 tons of food be-
tween the ages of 20 and 40. Since body weight will most
frequently be maintained at its set point or close to it, food
intake is finely controlled to within ±1% over time. A
1
% increase in food intake over this
2 0
-year period would
result in a 100-pound gain in weight. Both short-term reg-
ulation of starting and stopping of eating and long-term
regulation of total food intake occur. Both composition
and content are regulated. Different foods have different
energy contents. Thus, the amount of food eaten decreases
if it has a higher energy content per unit of weight; the
result is a constant energy intake.
After ingestion, food may either be stored or utilized,
with release of energy. Metabolic homeostasis requires a
balance between energy input and energy output. Energy
output occurs as heat produced, work produced, or main-
tenance of cellular integrity. These factors are balanced
by the signals for hunger, appetite, and satiety. Eating
starts and stops voluntarily in a manner that is not related
simply to body weight (short-term regulation) but also to
the need for energy and specific constituents (long-term
regulation).
Regulators of food intake, fuel stores, and energy bal-
ance are many and involve a complex set of physiological
signals. Some of the regulators are blood glucose level,
which is maintained by insulin and other counterregulatory
hormones, the mass of adipose tissue and the adipocyte-
derived hormone leptin, cerebral cortex and hypothalamic
neurons, hypothalamic-pituitary-adrenal axis, distention
of the gastrointestinal tract, and release of gastrointestinal
and gonadal hormones. The prevalence of overweight and
obesity are global health problems. The risk of death from
all causes is increased in both conditions and is discussed
later.
22.5 Carbohydrate Homeostasis
Most tissues can use fatty acids as their primary, if not
sole, source of metabolic energy. Brain and other nervous
tissues, except in long-term fasting use glucose as the sole
energy source; even in long-term fasting they require sig-
nificant amounts of glucose. Red blood cells can obtain
energy only by anaerobic glycolysis. Skeletal muscle at
rest uses predominantly fatty acids, but in heavy exercise
it also draws on muscle glycogen and blood glucose. Be-
cause brain and red blood cells depend on glucose for
energy, glucose must always be available.
Glucose occurs in plasma and interstitial fluid at a con-
centration of approximately 80 mg/dL; this value corre-
sponds to about
2 0
g in the extracellular compartment
of a typical person. Approximately 180 g of glucose is
oxidized per day. The body must therefore replenish the
total blood glucose concentration about nine times a day;
nevertheless, the concentration in blood remains remark-
ably constant. The glucose level following an overnight
fast is approximately 80 mg/dL. Following a meal, such
as breakfast, the level rapidly rises by 30-50 mg/dL, but
within
2
hours it returns to the previous level where it re-
mains until the next meal when the pattern is repeated.
The remarkable stability of the blood glucose level is an
indication of the balance between supply and utilization.
Maintenance of this balance is discussed below.
Carbohydrate as a Food
Carbohydrate is essential for the survival of some tissues
and as a structural constituent of nucleic acids, glyco-
proteins, proteoglycans, and glycolipids. The normal adult
can synthesize all the needed carbohydrate from noncarbo-
hydrate sources, namely, amino acids and glycerol. Thus,
