cells. When blood glucose concentration returns toward nor-
mal, glucagon secretion decreases
. This mecha-
nism prevents hypoglycemia from occurring at times when
glucose concentration is relatively low, such as between
meals, or when glucose is being used rapidly—during peri-
ods of exercise, for example.
is also a protein, and its main
effect is exactly opposite that of glucagon. Insulin stimulates
the liver to form glycogen from glucose and inhibits conver-
sion of noncarbohydrates into glucose. Insulin also has the
special effect of promoting the facilitated diffusion (see chap-
ter 3, p. 93) of glucose through the membranes of cells bear-
ing insulin receptors. These cells include those of cardiac
muscle, adipose tissues, and resting skeletal muscles (glu-
cose uptake by exercising skeletal muscles is not dependent
on insulin). Insulin action decreases the concentration of
blood glucose, promotes transport of amino acids into cells,
and increases protein synthesis. It also stimulates adipose
cells to synthesize and store fat.
An enzyme called glucokinase enables pancreatic cells to “sense” glu-
cose level, important information in determining rates of synthesis
of glucagon and insulin. One form of a rare type of diabetes mellitus,
maturity-onset diabetes of the young (MODY), is caused by a muta-
tion in a gene encoding glucokinase—the beta cells cannot accu-
rately assess when they must produce insulin. Other mutations that
cause MODY alter insulin’s structure, secretion, or cell surface recep-
tors or the ability of liver cells to form glycogen in response to insulin.
MODY is treated with drugs or dietary modiF
A negative feedback system sensitive to the concentra-
tion of blood glucose regulates insulin secretion. When glu-
cose concentration is relatively high, such as after a meal,
the beta cells release insulin. By promoting formation of gly-
cogen in the liver and entrance of glucose into adipose and
muscle cells, insulin helps prevent excessive rise in blood
glucose concentration (hyperglycemia). Then, when the glu-
cose concentration falls, between meals or during the night,
insulin secretion decreases (F
As insulin concentration falls, less glucose enters the
adipose and muscle cells, and the glucose remaining in the
blood is available for cells that lack insulin receptors, such
as nerve cells. Neurons readily tap the energy in a continu-
ous supply of glucose to produce ATP.
Hypoglycemia, or low blood glucose level due to excess insulin in the
bloodstream, causes episodes of shakiness, weakness, and anxiety.
±ollowing a diet of frequent, small meals low in carbohydrates and
high in protein can often control symptoms by preventing the surges
of insulin that lower the blood glucose level. Hypoglycemia is most
often seen when a person with diabetes injects too much insulin, but
it can also re²
ect a tumor of the insulin-producing cells of the pan-
creas, or it may occur transiently following strenuous exercise.
Common bile duct
(Islet of Langerhans)
The hormone-secreting cells of the pancreas are
grouped in clusters, or islets, closely associated with blood vessels.
Other pancreatic cells secrete digestive enzymes into ducts.
Pancreatic islet (Islet of Langerhans)
Light micrograph of pancreatic islets (200×).