Endocrine Metabolism III: Adrenal Glands
NE at the JGA of the kidney and this stimulates the re-
lease of renin (/?]), ultimately resulting in aldosterone-
mediated sodium retention at the nephron. The overall
result is preservation and promotion of vascular volume
due to isotonic fluid retention, decreased urine flow, and
decreased glomerular filtration rate, all of which are at-
tributable to neurotransmitted NE.
Paradoxically, elevated levels of E and NE can cause a
reduction in plasma volume that can lead to hemoconcen-
tration and poor tissue perfusion; however, the mechanism
of this effect is not known. This is said to be the cause of or-
thostatic hypotension in untreated patients with pheochro-
mocytoma, a tumor of chromaffin tissue that produces
excessive amounts of NE; most of these patients have re-
duced plasma volume but exhibit hypertension while in
the reclining position.
Metabolic, Endocrine, and Thermogenic Effects
E promotes the production and release of glucose from the
liver by two related mechanisms:
1. A direct stimulatory effect on hepatic glycogenolysis
mediated by cAMP-dependent phosphorylation
of phosphorylase. This effect is dependent on prior
storage of glycogen in the liver; therefore, both insulin
and cortisol serve to condition the liver for this effect.
2. A direct activation of gluconeogenesis in the liver
(/32) via cAMP-dependent phosphorylation of the key
gluconeogenic enzymes. This effect requires prior
induction and maintenance of enzyme concentrations
by cortisol.
These two glucose-generating actions of E on the liver
are enhanced in an additive fashion by glucagon which,
like E, depends on cAMP mediation and cortisol condi-
tioning. The fact that neural NE simultaneously causes a
fall in the insulin/glucagon ratio indicates that the sympa-
thetic nervous system has a supportive role.
Neural NE and plasma E are both stimulators of
adipocyte lipolysis, an effect that is mediated by /S,- and
/?3-adrenergic receptors and involves cAMP-mediated
phosphorylation of hormone-sensitive lipase (HSL). There
are regional differences in /
3-adrenergic receptor den-
sity (visceral fat has more than subcutaneous fat), which
determines that catecholamine is physiologically impor-
tant. Note that /3
receptors are low-affinity receptors that
require high concentrations of catecholamines. They re-
spond better to neural stimulation because of the higher
local concentration of NE at the fat tissue site.
Cortisol, thyroid hormone, and GH support this effect
of the catecholamines, presumably by promoting the syn-
thesis of one or more components of the lipolytic pathway.
This results in the release of free fatty acids (FFAs) and
glycerol. Glycerol is taken up by the liver and is used for
the production of glucose via gluconeogenesis (/32)- FFAs
are taken up by cardiac muscle, skeletal muscle, kidney,
and liver, and are oxidized for energy which obliges these
tissues to consume less glucose. In the liver, where FFA
uptake is related to circulating FFA levels, the oxidation of
acyl-coA also is shunted to ketogenesis; ketone body pro-
duction increases as a result (Chapter 18). E can promote
FFA utilization and ketogenesis in the liver by inhibit-
ing acetyl-CoA carboxylase activity
2)l this results in
unrestricted entry of FFA into the mitochondria for oxida-
tion and subsequent ketogenesis. Ketone bodies are con-
sumed by extrahepatic tissues that possess succinyl-CoA-
acetoacetate-CoA transferase, also known as thiophorase
(cardiac muscle, skeletal muscle, intestines, kidney, and
the brain during starvation), and this also has a glucose-
sparing effect.
E stimulates skeletal muscle glycogenolysis
thus promotes glycolysis. The effects of E may depend
on skeletal muscle activity because contraction alone is a
stimulus of both glycogenolysis and glycolysis; the effects
may also be influenced by the muscle fiber type (types I,
Ila, or lib). In resting muscle and presumably in type I
(slow-twitch) fibers, there is preferential use of fatty acids
and ketone bodies for energy, which also inhibits glycol-
ysis; thus, the glycogenolytic and glycolytic effects of E
may be minimal or overriden. In the contracting muscle
and presumably in fast-twitch (types Ila and lib) fibers,
E may potentiate the active glycogenolytic and glycolytic
pathways and promote the release of both lactate and ala-
nine. Indirectly, E can inhibit skeletal muscle glycolysis
by increasing the supply of FFAs and ketone bodies, which
are glucose-sparing energy fuels for this tissue; however,
the increased turnover of ATP in the contracting muscle
probably allows the tissue to accommodate both glucose
and fatty acids as fuels (Chapter 21).
A potentially harmful effect is the stimulation by E of
potassium ion movement from plasma into skeletal muscle
and liver (/12), which can lead to
This effect
is accompanied by a decrease in potassium ion excretion
by the kidney. The ability of E to stimulate plasma mem-
brane Na+,K+-ATPase activity in skeletal muscle (/J2)
may partially explain this hypokalemic action, as well as
the thermogenic effect of the hormone (see below).
The direct adrenergic innervation of the islets of Langer-
hans in the pancreas allows NE to stimulate the release
of glucagon from the
cells (/J2) and to inhibit the re-
lease of insulin from the
causing the in-
sulimglucagon (I:G) ratio to fall. Circulating E also exerts
these effects and is probably important in maintaining the
low I:G ratio following neural stimulation. Because the
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