518
chapter 22
Metabolic Homeostasis
it is superseded by fatty acid and plasma glucose utiliza-
tion. Most of the plasma glucose used is oxidized entirely
but 10-20% is converted to lactate. During the exercise
and depending on the past dietary history, branched-chain
amino acid oxidation contributes some energy, and alanine
is formed to eliminate the a-amino nitrogen. Lactate and
alanine are used in the liver for gluconeogenesis and can
provide 5-15% of the glucose required by skeletal mus-
cle. The rest of the glucose is derived from glycogenoly-
sis. Thus, in endurance exercise, hepatic glycogen serves
as a major fuel for muscle, and muscle glycogen is the
initial fuel. As plasma glucose and fatty acids are used,
glycogenolysis in muscle diminishes; despite its smaller
contribution, muscle glycogen plays a critical role since
exhaustion occurs with its total depletion in spite of
the availability of fatty acids and plasma glucose. Thus,
“glycogen loading” is used to extend endurance. Exercise-
depleted glycogen stores can be increased to above-normal
levels for about 24 hours by high-carbohydrate refeeding.
With elevated levels of tissue glycogen, an individual’s
endurance ability is increased. Several other phenomena
contribute to the pattern of metabolite utilization in high-
intensity endurance exercise.
1. Although fatty acids are avidly utilized by skeletal
muscle during exercise, their plasma concentrations
do not differ significantly from those at rest. Their
utilization is being balanced by production from
adipocyte lipolysis, probably as a result of an elevated
catecholamine level.
2. Glucose uptake by skeletal muscle increases with
intensity of exercise even though levels of circulating
insulin decrease. Either this glucose transport is
insulin-independent or exercise enhances insulin
sensitivity.
3. The increase in glucose uptake with increased
intensity of exercise is matched by hepatic glucose
production to the extent that arterial glucose
concentrations are elevated by very intense exercise.
Hepatic glycogenolysis probably is enhanced by a
decrease in the level of insulin and by an increase in
levels of glucagon and epinephrine.
4. Exercise may lower insulin levels even though plasma
glucose concentrations are increased. This effect may
result from a-adrenergic inhibition of /3-cell secretion.
Low-Level Nonfatiguing Exercise
This exercise is characteristic of an individual in normal
occupational tasks that could reasonably be continued for
8-12 hours. The principal substrates used are similar to
those in long endurance exercise but without depletion
of phosphocreatine and with minimal muscle glycogen
utilization. The main source of energy is the aerobic oxi-
dation of fatty acids, glucose, and branched-chain amino
acids.
Supplemental Readings and References
P. H. Bennett, S. Haffner, B. Kasiske, et al.: Diabetic renal disease recom-
mendations.
A m e rica n Jo u rn a l o f K id n ey D isea se
25, 107 (1995).
E. E. Calle, M. J. Thun, J. M. Petrelli, et al.: Body-mass index and mortality
in a prospective cohort of U.S. adults.
N ew E n g la n d J o u rn a l o f M ed icin e
341,
1097(1999).
G. W. Cline, K. F. Petersen, M. Krssak, et al.: Impaired glucose trans-
port as a cause of decreased insulin-stimulated muscle glycogen syn-
thesis in type 2 diabetes.
N ew E n g la n d J o u rn a l o f M ed icin e
341,
240
(1999).
S. Dagogo-Jack and J. V. Santiago: Pathophysiology of type 2 diabetes
and modes of action of therapeutic interventions.
A rch ives o f In tern a l
M ed icin e
157,
1802 (1997).
R. DeFronzo: Pharmacologic therapy for type 2 diabetes mellitus.
A n n a ls o f
In tern a l M ed icin e
131,
281 (1999).
Expert Committee on the Diagnosis and Classification of Diabetes Mellitus:
Report of the expert committee on the diagnosis and classification of
diabetes mellitus.
D ia b etes C are
20, 1183 (1997).
I. S. Farooqi, S. A. Jebb, G. Langmack, et al.: Effects of recombinant leptin
therapy in a child with congenital leptin deficiency.
N ew E n g la n d Jo u rn a l
o f M ed icin e
341,
879 (1999).
F. L. Ferris III, M. D. Davis, and L. W. Aiello: Treatment of diabetic retinopa-
thy.
N ew E n g la n d J o u rn a l o f M ed icin e
341,
667 (1999).
J. M. Friedman and J. L. Halaas: Leptin and the regulation of body weight
in mammals.
N a tu re
395,
763 (1998).
B. Glaser, P. Kesavan, M. Heyman, et al.: Familial hyperinsulinism caused
by an activating glucokinase mutation.
N ew E n g la n d J o u rn a l o f M ed icin e
338,
226(1998).
S. B. Heymsfield, A. S. Greenberg, K. Fujioka, et al.: Recombinant leptin
for weight loss in obese and lean adults.
J o u rn a l o f A m erica n M ed ica l
A sso cia tio n
282,
1568 (1997).
F. Holleman and J. B. L. Hoekstra: Insulin lispro.
N ew E n g la n d Jo u rn a l o f
M ed icin e
337,
176(1997).
S. J. Hunter and W. T. Garvey: Insulin action and insulin resistance: dis-
eases involving defects in insulin receptors signal transduction, and the
glucose transport effector system.
A m e rica n J o u rn a l o f M ed icin e
105,
331
(1998).
S. L. Kjos and T. A. Buchanan: Gestational diabetes mellitus.
N ew E n g la n d
J o u rn a l o f M ed icin e
341,
1749 (1999).
A. Must, J. Sadano, E. H. Coakley, et al.: The disease burden associated with
overweight and obesity.
J o u rn a l o f A m e rica n M ed ica l A sso cia tio n
282,
1523(1999).
O. E. Owen, K. J. Smalley, D. A. D’Alessio, et al.: Protein, fat, and car-
bohydrate requirements during starvation: anaplerosis and cataplerosis
A m erica n J o u rn a l o f C lin ica l N u tritio n
6 8
, 12 (1998).
A. Rebollo and C. Martinez-A:
R a s
protein: recent advances and new func-
tions.
B lo o d
94,
2971 (1999).
M. Ristow, D. Miller-Wieland, A. Pfeiffer, et al.: Obesity associated with a
mutation in a genetic regulator of adipocyte differentiation.
N ew E n g la n d
J o u rn a l o f M ed ic in e
339,
953 (1998).
E. Ritz and S. R. Orth: Nephropathy in patients with type 2 diabetes mellitus.
N ew E n g la n d J o u rn a l o f M ed icin e
341,
1127 (1999).
J. N. Roemmich and A. D. Rogol: Role of leptin during childhood growth and
development.
E n d o c rin o lo g y a n d M e ta b o lism C lin ics o f N o rth A m erica
28,
749 (1999).
