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The Pancreas

The pancreas has two roles: It functions both as an endocrine and as an exocrine organ. As an
exocrine organ, the pancreas releases digestive enzymes via a small duct into the small intestine.
These enzymes break down carbohydrates, fats, and proteins from food that has been partially
digested by the stomach. The exocrine pancreas also releases a bicarbonate to neutralize stomach
acid in the duodenum (first portion) of the small intestine.
In its role as an endocrine organ, the pancreas secretes the hormones insulin and glucagon, which
help the body use and store its primary source of energy—glucose (sugar). The endocrine
pancreas also secretes somatostatin, which is a primary regulator of insulin and glucagon release.
The pancreas is long and soft, and stretches from the duodenum of the small intestine almost to
the spleen. It is divided into a head (its widest point), neck, body, and tail. The endocrine pancreas
is made up of clusters of cells called the islets of Langerhans, in which the hormones insulin and
glucagon are produced. There are about one million islets, but they make up only about 1 percent
of the endocrine pancreas’ total volume. The islets also contain parasympathetic and sympathetic
neurons, which influence insulin and glucagon secretion. The islets also produce the hormones
somatostatin and pancreatic polypeptide.

Energy Metabolism
Why are insulin and glucagon so crucial? Because the body needs energy to survive, and these
two hormones regulate the distribution of energy to tissues. Energy enters the body in the form
of food. As food passes through the mouth, esophagus, and stomach, enzymes break it down into
tiny pieces. Once the partially digested food reaches the intestines, more enzymes go to work,
breaking it down into molecules small enough to enter the bloodstream and be transported to
cells. Starches are broken down into glucose (sugar), proteins are broken down into amino acids,
and fats are broken down into fatty acids and glycerol.
Food metabolism occurs in two distinct phases: During the anabolic phase, which occurs after a
meal, enzymes convert nutrients from food into substances the body can use. Blood levels of
glucose, fatty acids, and amino acids rise. Because the body has more energy than it needs at the
moment, it stores the excess for later. Glucose is stored as glycogen in the liver and muscles, fat
is stored in adipose tissue, and amino acids are stored in muscle.
About four to six hours after a meal, the catabolic phase begins. Stored energy from the liver,
muscles, and adipose tissue is mobilized to sustain the body until its next meal. The liver produces
glucose from stored glycogen and by converting amino acids via gluconeogenesis. When the body
has gone for some time without food, the liver converts free fatty acids into ketone bodies. The
brain normally uses only glucose for energy, but it can use ketone bodies as a backup energy
source when glucose supplies are low. Without this alternative energy source, the brain and
nervous system would starve and suffer permanent damage.
The hormones insulin and glucagon from the endocrine pancreas regulate these stages of energy
metabolism. Insulin primarily regulates the anabolic phase, while glucagon influences the
catabolic stage.

After a meal, the body converts carbohydrates from foods into simple sugars in the intestine.
Glucose is carried to the tissues through the bloodstream. When blood glucose levels rise, the
beta cells in the endocrine pancreas produce and release insulin. Insulin is formed from a larger,
inactive molecule, called proinsulin. Before insulin is released into the bloodstream, the inactive
molecule splits off. For a look at diabetes, a chronic condition involving insulin production, see
Sidebar 4.1.
Insulin levels rise 8–10 minutes after a meal, reaching their peak concentration 30–45 minutes
after the meal. Nearly every cell in the body has insulin receptors. When insulin binds to its
receptors on the cell surface, it triggers other receptors that help the cells take in glucose. The
body uses and stores glucose in the liver, muscles, and adipose tissues. Without insulin, an
individual could eat three meals a day and still starve to death because the cells would be unable
to use the energy.
In the liver, insulin promotes glucose storage in the form of glycogen. It also inhibits the
breakdown of glycogen and the production of glucose from other, no carbohydrate sources
(gluconeogenesis), and it decreases overall glucose release by the liver.
Insulin helps transport glucose to muscle cells and stimulates the incorporation of amino acids
into protein, which is used to sustain and repair muscles. It promotes glycogen synthesis to replace
glucose the muscles have used. Insulin also promotes glucose uptake in adipose tissue, promotes
its conversion to fatty acids, and inhibits the release of stored fatty acids.
As insulin moves glucose into the tissues for energy use and storage, blood glucose levels fall.
Between 90 and 120 minutes after a meal, blood glucose concentration returns to its original, pre-
meal levels. To help the body maintain a constant blood glucose level, insulin and glucagon
release are synchronized on an alternate schedule. When glucose concentrations in the blood rise
during the anabolic phase, insulin is released. As insulin pulls glucose from the blood for tissue
use and storage, blood glucose concentrations drop, stimulating glucagon release.
Insulin release may also be triggered by signals from the nervous system in response to external
stimulation; for example, the sight and/or smell of food. The gastrointestinal hormones
cholecystokinin (CCK), secretin, gastrin, gastric inhibitory peptide (GIP), and acetylcholine are
thought to play a role in this response, preparing the pancreas to release insulin. Insulin release is
inhibited not only by low glucose levels, but also by low levels of amino acids and fatty acids in
the blood, as well as by the hormones somatostatin, epinephrine, and leptin.
Following a meal, insulin pulls glucose from the blood to be used and stored by cells. When
several hours have passed without additional food being ingested, blood sugar is eventually
depleted (a condition called hypoglycemia). The body still needs energy, much of which it gets
from fatty acids until the next meal is available. But the brain, which cannot directly use fatty
acids and other alternative energy sources, still relies on glucose. In response to dropping blood
glucose levels, the alpha (α) cells of the endocrine pancreas begin to secrete the hormone glucagon
from the large precursor molecule proglucagon. The same prohormone is found in cells of the
gastrointestinal system, although it produces different secreted products.
Glucagon has the opposite effect of insulin. Whereas insulin lowers blood glucose levels by
promoting glucose usage and storage, glucagon raises blood glucose levels. It acts primarily upon
the liver to increase glucose output. When it binds to receptors on liver cells, glucagon activates
the enzymes that break down stored glycogen (glycogenolysis) to release glucose and increases
production of glucose from amino acid precursors (a process called gluconeogenesis). In adipose
tissue, glucagon promotes the breakdown and release of fatty acids (lipolysis) into the blood,
which are used by the cells for energy in the absence of glucose. By raising the level of fatty acids
in the blood, glucagon indirectly prevents glucose uptake by the muscles and adipose tissue.
The main trigger for glucagon release is low blood sugar, but it may also be stimulated by other
hormones, namely the catecholamine’s (in stressful situations); cholecystokinin, gastrin, and
gastric inhibitory peptide (GIP) from the gastrointestinal system; and the glucocorticoids.
Sympathetic nerve stimulation can also lead to glucagon release. Rising blood glucose levels,
high circulating levels of fatty acids, as well as the hormones insulin and somatostatin inhibit
glucagon secretion.

Understanding Diabetes: The Key to Staying Healthy

Diabetes is a serious, chronic condition involving the endocrine system. It is defined as a disease
where patients have elevated levels of blood glucose or sugar that results from defects in either
or both insulin production and action. According to the most recent estimates from the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 23.6 million people—over 7
percent of the population—have diabetes. Of particular concern is that of these over 20 million
people with diabetes, almost 6 million are undiagnosed. This is especially dangerous because
diabetes can lead to serious complication—even premature death—if patients do not control the
disease and lower the risk of complications. There are three primary types of diabetes, and below
is a brief explanation of each of these types:
 Type 1 Diabetes: Formerly known as insulin-dependent diabetes mellitus or juvenile-onset
diabetes, type 1 diabetes occurs when the body’s immune system destroys the cells in the
body—called pancreatic beta cells—that produce insulin that regulates blood glucose
levels. Patients with this type of diabetes use either a pump or injection device to deliver
insulin into their body. While type 1 diabetes typically develops in children and young
adults, it can develop in people of any age. In fact, type 1 diabetes accounts for 5–10 percent
of all diagnosed cases of diabetes. There is currently no known way to prevent this type
the diabetes. Some risk factors are believed to be linked to autoimmune, genetic, or
environmental factors.

 Type 2 Diabetes: Formerly known as non-insulin-dependent diabetes mellitus, this type

of the disease is estimated to comprise 90–95 percent of all diagnosed cases of diabetes in
adults. Diagnosis is typically preceded by an inability of the cells to properly produce
insulin—a condition known as insulin resistance. The need for insulin steadily increases
while the pancreas generally loses the ability to produce it.

This type of diabetes has several known risk factors: older age, obesity, family history of
the disease, and lack of physical activity. In addition, experts believe that race/ethnicity
can be a risk factor. Medical experts believe that African Americans, Hispanic/Latino
Americans, Native Americans, and some Asian Americans and Native Hawaiians or other
Pacific Islanders have an increased risk for type 2 diabetes.

 Gestational Diabetes: This type of diabetes is related to glucose intolerance and is

diagnosed in pregnant women — occurring more frequently among African American,
Hispanic/Latino American, and Native American women. Obesity and family history are
also risk factors for diabetes. During pregnancy, treatment is focused on normalizing
glucose levels to protect the infant. After pregnancy, however, an estimated 5–10 percent
of women with gestational diabetes are diagnosed with type 2 diabetes. In addition, women
with gestational diabetes are at an increased chance—40–60 percent—of developing type
2 diabetes over the next 5–10 years.
If not treated and controlled properly, diabetes can lead to serious complications, including
blindness, kidney damage, cardiovascular disease, and amputations of lower limbs. The risk of
these complications can be lowered by controlling blood glucose, blood pressure, and blood lipid
levels. As mentioned earlier, many type 1 and 2 diabetes patients need insulin delivered by
injection or a pump. Some patients also have to take other medications to control related
conditions, such as high blood pressure. However, some patients take little or no medications—
even insulin—by following a healthy meal and exercise plan. According to the NIDDK, among
adults with type 1 or 2 diabetes, an estimated 14 percent take only insulin, 13 percent take both
insulin and oral medication, 57 percent take oral medication only, and 16 percent do not take
either insulin or oral medication. The treatment regimen for each individual will often change
over the course of the disease. Among diagnosed diabetics—type 1 or type 2—14 percent take
insulin only, 13 percent take both insulin and oral medication, 57 percent take oral medication
only, and 16 percent do not take either insulin or oral medication. Medications for each individual
with diabetes will often change over the course of the disease.