Ganong's Review of Medical Physiology, 23rd Edition

(Chris Devlin) #1
CHAPTER 21Endocrine Functions of the Pancreas & Regulation of Carbohydrate Metabolism 325

tion, and hyperosmolarity on the nervous system and dies if
treatment is not instituted.
All of these abnormalities are corrected by administration
of insulin. Although emergency treatment of acidosis also
includes administration of alkali to combat the acidosis and
parenteral water, Na+, and K+ to replenish body stores, only
insulin repairs the fundamental defects in a way that permits
a return to normal.


INSULIN EXCESS


SYMPTOMS


All the known consequences of insulin excess are manifesta-
tions, directly or indirectly, of the effects of hypoglycemia on
the nervous system. Except in individuals who have been fast-
ing for some time, glucose is the only fuel used in appreciable
quantities by the brain. The carbohydrate reserves in neural
tissue are very limited and normal function depends on a con-
tinuous glucose supply. As the plasma glucose level falls, the
first symptoms are palpitations, sweating, and nervousness
due to autonomic discharge. These appear at plasma glucose
values slightly lower than the value at which autonomic acti-
vation first begins, because the threshold for symptoms is
slightly above the threshold for initial activation. At lower
plasma glucose levels, so-called neuroglycopenic symptoms
begin to appear. These include hunger as well as confusion
and the other cognitive abnormalities. At even lower plasma
glucose levels, lethargy, coma, convulsions, and eventually
death occur. Obviously, the onset of hypoglycemic symptoms
calls for prompt treatment with glucose or glucose-containing
drinks such as orange juice. Although a dramatic disappear-
ance of symptoms is the usual response, abnormalities ranging
from intellectual dulling to coma may persist if the hypoglyce-
mia was severe or prolonged.


COMPENSATORY MECHANISMS


One important compensation for hypoglycemia is cessation of
the secretion of endogenous insulin. Inhibition of insulin se-
cretion is complete at a plasma glucose level of about 80 mg/
dL (Figures 21–10 and 21–11). In addition, hypoglycemia trig-
gers increased secretion of at least four counter-regulatory
hormones: glucagon, epinephrine, growth hormone, and cor-
tisol. The epinephrine response is reduced during sleep. Glu-
cagon and epinephrine increase the hepatic output of glucose
by increasing glycogenolysis. Growth hormone decreases the

FIGURE 21–9 Effects of insulin deficiency. (Courtesy of RJ Havel.)


Insulin deficiency
(and glucagon excess)

Increased
protein
catabolism

Dehydration,
acidosis

Decreased
glucose
uptake

Increased
lipolysis

Increased
plasma
amino acids,
nitrogen loss
in urine

Coma,
death

Hyperglycemia,
glycosuria,
osmotic diuresis,
electrolyte
depletion

Increased
plasma FFA,
ketogenesis,
ketonuria,
ketonemia

FIGURE 21–10 Plasma glucose levels at which various
effects of hypoglycemia appear.

FIGURE 21–11 Mean rates of insulin and glucagon delivery
from an artificial pancreas at various plasma glucose levels. The
device was programmed to establish and maintain various plasma glu-
cose levels in insulin-requiring diabetic humans, and the values for
hormone output approximate the output of the normal human pan-
creas. The shape of the insulin curve also resembles the insulin re-
sponse of incubated B cells to graded concentrations of glucose.
(Reproduced with permission from Marliss EB, et al: Normalization of glycemia in
diabetics during meals with insulin and glucagon delivery by the artificial pancreas.
Diabetes 19 77 ;26:663.)

Plasma glucose
mmol/L mg/dL
90

75

60

45

30

15

0

4.6 Inhibition of insulin secretion

Glucagon, epinephrine, growth
hormone secretion
Cortisol secretion
Cognitive dysfunction

Lethargy
Coma
Convulsions

Permanent brain damage, death

0

1.1

0.6

1.7

2.8

2.2

3.2

3.8

4.50

3.00

1.50

0
40 80 120160 200 240

500
400

300

200
100

Glucagon

Insulin

Plasma glucose (mg/dL)

Glucagon secretion rate


g/min)

Insulin secretion rate

(mU/min)
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