Page 302 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Hyperinsulinism, Hypoglycemia
Insulin release is, first and foremost, regulated tions of amino acids in blood are markedly
by glucose (→ A1). Glucose is taken up by the raised (e.g., in hyperleucinemia). The insulin
beta cells of the pancreas and metabolized in release stimulated by the amino acids is then
them. The resulting ATP inhibits the ATP-sen- too high for the particular glucose concentra-
+
sitive K channels. Subsequent depolarization tion and hypoglycemia results. In liver failure
opens voltage-dependent Ca 2+ channels so the reduced breakdown of amino acids can
that Ca 2+ enters the cell. The rise in intracellu- cause hypoglycemia (→ A2). Abnormalities of
lar Ca 2+ concentration then triggers insulin re- carbohydrate metabolism (→ p. 244), such as
lease. The sulfonylureas used as oral antidia- some glycogen storage diseases, fructose intol-
betic drugs stimulate the release of insulin by erance or galactosemia, can also bring about
+
directly inhibiting the ATP-sensitive K chan- hypoglycemia.
nels. In the dumping syndrome after a gastric re-
Insulin release is stimulated not only by section, sugar taken orally reaches the gut
glucose but also by amino acids (→ A2) and a without delay, abruptly stimulates the release
number of gastrointestinal hormones (gluca- of gastrointestinal hormones, and is quickly
gon, secretin, gastrin, glucose-dependent insu- absorbed. The gastrointestinal hormones and
Hormones nin [CCK]) as well as by somatotropin. The ac- to an excessive release of insulin, so that hypo-
the steeply rising glucose concentration lead
lin-releasing peptide [GIP], and cholecystoki-
tion of gastrointestinal hormones is responsi-
glycemia occurs after an interval of one to two
In rare cases an excess of insulin is caused
sults in a greater insulin release than the
9 ble for the fact that oral intake of glucose re- hours (→ p.148).
same amount of glucose introduced parenter- by an insulin-producing tumor (→ A3).
ally. Relative insulin excess can also occur with
Insulin excess is usually the result of too normal insulin release if the release and/or
high a dose of insulin or of an oral antidiabetic the action of the insulin-antagonistic hor-
drug during treatment of diabetes mellitus mones (glucocorticoids, epinephrine, gluca-
(→ A3). As a rule overdosage becomes mani- gon, somatotropin) is impaired. This is espe-
fest when insulin requirement falls on physical cially so if the glucose reserves are low and
activity. Insulin excess also often occurs in gluconeogenesis from amino acids is limited,
newborn babies of diabetic mothers (→ A4). as in liver failure, after starvation or alcohol-
The high glucose and amino acid concentra- ism, but also on increased glucose utilization,
tions in the mother’s blood will lead intrauter- as during heavy work or in tumors (→ A5).
inely to stimulation and hyperplasia of the The most important effect of absolute or
child’s beta cells, so that after birth an inappro- relative insulin excess is hypoglycemia, which
priately large amount of insulin is released. causes a voracious appetite and leads to mas-
In some people insulin release is delayed, so sive sympathetic nervous stimulation with
that the hyperglycemia that develops after the tachycardia, sweating, and tremors (→ A6).
intake of a carbohydrate-rich meal is especial- The impaired energy supply of the nervous
ly marked. This results in an overshoot of insu- system, which requires glucose, can result in
lin release, which after four to five hours seizures and loss of consciousness. Ultimately,
causes hypoglycemia. Frequently such patients the brain may be irreversibly damaged.
later develop diabetes.
In rare cases hypoglycemia is caused by in-
sulin-binding autoantibodies. As a result, insu-
lin is released with some delay from its bind-
ing to the antibodies. In even rarer cases, stim-
ulating autoantibodies against the insulin re-
ceptors can produce hypoglycemia.
292 In a number of, altogether rare, genetic de-
fects of amino acid breakdown the concentra-
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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