Ganong's Review of Medical Physiology, 23rd Edition

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

(μ

g/min)

Insulin secretion rate

(mU/min)