496
chapter
22
Metabolic Homeostasis
(of the same or different types). Glucagon secretion is
also stimulated by
gastrin
and cholecystokinin, presum-
ably as an anticipatory response to intestinal fuel ab-
sorption. Stress and catecholamines provoke glucagon
secretion, which increases output of hepatic glucose and
adipocyte fatty acids to provide the extra energy require-
ments.
The primary targets for glucagon are the liver and adi-
pose tissue. It stimulates hepatic glycogenolysis, gluco-
neogenesis, and ketogenesis and inhibits glycogen syn-
thesis. Glucagon stimulates adipocyte lipolysis to provide
fatty acids to tissues for which glucose is not the obligatory
fuel. In both liver and adipose tissues, glucagon activates
adenylate cyclase, increases cAMP level, activates cAMP-
dependent protein kinase, and increases phosphorylation
of the controlling enzymes in the various metabolic path-
ways (Chapter 15).The initial step in the glucagon sig-
naling pathway involves its binding to the receptor on
the cell membrane and activation of G-protein complex
(Chapter 30).
The major function of insulin and glucagon is to
maintain
fuel
homeostasis.
Since
glucagon
opposes
the actions of insulin, the
[insulin]/[glucagon]
ratio
determines
the
metabolic
fate
of fuels
due
to
the
induction or repression of appropriate enzymes. En-
zymes
induced by
a high
[insulin]/[glucagon]
ratio
and repressed by a low ratio are glucokinase, citrate
cleavage enzyme, acetyl-CoA carboxylase, /3-hydroxy-
/1-methylglutaryl-CoA (HMG-CoA) reductase, pyruvate
kinase,
6
-phosphofructo
- 1
-kinase,
6
-phosphofructo-
2
-
kinase, and fructose-2,
6
-bisphosphatase. Enzymes in-
duced by a low [insulin]/[glucagon] ratio and repressed by
a high ratio are glucose-
6
-phosphatase, phosphoenolpyru-
vate
carboxykinase,
and
fructose-
1
,
6
-bisphosphatase.
Metabolic implications of these actions are discussed
later.
Somatostatin
Two forms of somatostatin exist: S14 and S28, which are
single-chain polypeptides of 14 and 28 amino acids, re-
spectively. Somatostatin is synthesized in the
S
cells of the
islets, the gut, the hypothalamus, and several other areas
of the brain. Its actions appear to be primarily paracrine in
nature (i.e., on other cell types in the immediate vicinity of
its secretion). In the islets it blocks insulin and glucagon
secretion; in the pituitary gland it inhibits growth hormone
and thyroid-stimulating hormone (TSH) release; in the gut
it blocks secretion of gastrin and motilin, inhibits gastric
acid and pepsin secretion, and suppresses gallbladder con-
traction. The action of somatostatin on the gastrointesti-
nal tract leads to decreased delivery of nutrients to the
circulation.
Pancreatic Polypeptide
Pancreatic polypeptide, a peptide of 36 amino acids, is se-
creted in response to fuel ingestion and potentially affects
pancreatic exocrine secretion of bicarbonate and protein.
22.4 Stored Fuels
Table 22-2 lists the amounts of fuels stored in the hu-
man body. The amount of glycogen present would not
suffice for even 1
day of normal energy expenditure. Tri-
acylglycerol and protein are the principal energy stores,
with lipid being in highest abundance. Although glu-
cose, amino acids, fatty acids, and triacylglycerols are
present in body fluids, their amounts would not support
life for 1
hour. Glycogen is rapidly mobilized in the first
24—36 hours of fasting; little is mobilized after the
fourth day of fast. Protein degradation starts off at a
TABLE 22-2
Metabolic Fuels Stored in a Normal 70-kg Human
*
Tissues
Wt(kg)
Available Energy kcal(kj)
Triacylglycerol (adipose tissue)
15
141,000 (589,944)
Glycogen (liver and muscle)
0.4
1,500 (6,276)
Protein (primarily muscle)
6
24,000 (100,416)
Extracellular Fluids
Glucose
0 . 0 2
80 (335)
Lipid (fatty acid and triacylglycerol)'1
'
0.05
400 (1,674)
Amino acids
0.03
120 (502)
*Data from G. F. Cahill: Starvation in man.
N . E n g l . J . M e d .
282,668 (1970).
tTotal lipid varies from this level down to 0.005 kg between periods of eating and fasting.
