REVIEW OF ANATOMY AND PHYSIOLOGY

Pancreas
The pancreas is a long, slender organ, most of which is located posterior to the bottom half of the stomach.
Although it is primarily an exocrine gland, secreting a variety of digestive enzymes, the pancreas also has
endocrine cells. Its pancreatic islets—clusters of cells formerly known as the islets of Langerhans—secrete
the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide (PP). The pancreas serves two
functions, endocrine and exocrine. The exocrine function of the pancreas is involved in digestion, and these
associated structures are known as the pancreatic acini. The pancreatic acini are clusters of cells that
produce digestive enzymes and secretions and make up the bulk of the pancreas. The endocrine function
of the pancreas helps maintain blood glucose levels, and the structures involved are known as the
pancreatic islets or the islets of Langerhans.

Types of Cells in the Pancreas

Pancreatic Cells
The pancreas is a glandular organ found in vertebrates that functions in both the digestive and endocrine
systems. It is an endocrine gland that generates insulin, glucagon, somatostatin, and pancreatic
polypeptide, among other substances. It's also an exocrine digestive organ that produces pancreatic juice,
which includes digestive enzymes to aid digestion and nutrition absorption in the small intestine. These
enzymes aid in the breakdown of the chyme's carbohydrates, proteins, and lipids. Staining slices of the
pancreas reveal two types of parenchymal tissue under a microscope. Islets of Langerhans are light-
stained clusters of cells that produce hormones that underpin the pancreas' endocrine functions. Acini,
which are attached to ducts, are formed by the dark-stained cells. Acinar cells are exocrine pancreas cells
that discharge digestive enzymes into the intestine via a duct system.
Islets of Langerhans
The pancreatic islets are small islands of cells that produce hormones that regulate blood glucose levels.
Hormones produced in the pancreatic islets are secreted directly into the blood flow by five different types
of cells. The endocrine cell subsets are:
 Alpha cells produce glucagon and make up 15–20% of total islet cells. Glucagon is a hormone
that raises blood glucose levels by stimulating the liver to convert its glycogen into glucose.
 Beta cells produce insulin and amylin and makeup 65–80% of the total islet cells. Insulin lowers
blood glucose levels by stimulating cells to take up glucose out of the bloodstream. Amylin slows
gastric emptying, preventing spikes in blood glucose levels.
 Delta cells produce somatostatin and makeup 3–10% of the total islet cells. Somatostatin is a
hormone that suppresses the release of the other hormones made in the pancreas.
 Gamma cells produce pancreatic polypeptides and make up 3–5% of the total islet cells.
Pancreatic polypeptide regulates both the endocrine and exocrine pancreatic secretions.
 Epsilon cells produce ghrelin and make up less than 1% of the total islet cells. Ghrelin is a protein
that stimulates hunger.
The feedback system of the pancreatic islets is paracrine—it is based on the activation and inhibition of the
islet cells by the endocrine hormones produced in the islets. Insulin activates beta cells and inhibits alpha
cells, while glucagon activates alpha cells, which activates beta cells and delta cells. Somatostatin inhibits
the activity of alpha cells and beta cells.

Pancreatic tissue: The small cells in Islet of Langerhans: A porcine islet of

the middle are beta cells, and the
surrounding larger cells are alpha,
delta, gamma, and epsilon cells.
Langerhans. On the left is a brightfield image
created using hematoxylin stain; nuclei are dark
circles and the acinar pancreatic tissue is darker
than the islet tissue. The right image is the same
section stained by immunofluorescence against
insulin, indicating beta cells.
The islets of Langerhans can influence each other through paracrine and autocrine communication. The
paracrine feedback system is based on the following correlations:
 The insulin hormone activates beta cells and inhibits alpha cells.
 The hormone glucagon activates alpha cells which then activate beta cells and delta cells.
 Somatostatin hormone inhibits alpha cells and beta cells.

Regulation of Blood Glucose Levels by Insulin and Glucagon

Glucose is used as a fuel for body cells during cellular respiration. The breakdown of carbohydrate-
containing foods and beverages provides glucose to the organism. Not immediately used for fuel, glucose
can be stored as glycogen in the liver and muscles, or converted to triglycerides and stored in adipose
tissue. Hormones control the storage and utilization of glucose in the body. The pancreas has receptors
that detect blood glucose levels, and the pancreatic cells then release glucagon or insulin to keep blood
glucose levels in check.
Glucagon
Glucagon is produced by alpha cells in the pancreas and elevates the concentration of glucose in the blood
by promoting gluconeogenesis and glycogenolysis. Glucose is stored in the liver in the form of the
polysaccharide glycogen, which is a glucan.
Liver cells have glucagon receptors and when glucagon binds to the liver cells they convert glycogen into
individual glucose molecules and release them into the bloodstream—this process is known as
glycogenolysis. As these stores become depleted, glucagon then encourages the liver and kidney to
synthesize additional glucose by gluconeogenesis. Glucagon also turns off glycolysis in the liver, causing
glycolytic intermediates to be shuttled to gluconeogenesis that can induce lipolysis to produce glucose from
fat.

Glucagon staining: This is an image from a

microscope stained for glucagon.
Receptors in the pancreas can sense the decline in blood glucose levels, such as during periods of fasting
or during prolonged labor or exercise. In response, the alpha cells of the pancreas secrete the
hormone glucagon, which has several effects:
 Glucagon stimulates the liver to convert its stores of glycogen back into glucose. This response is
known as glycogenolysis. The glucose is then released into the circulation for use by cells
throughout the body.
 Glucagon stimulates the liver to take up amino acids from the blood and convert them into glucose.
This response is known as gluconeogenesis.
 Glucagon stimulates lipolysis, the breakdown of stored triglycerides into free fatty acids and
glycerol. Some of the free glycerol released into the bloodstream travels to the liver, which converts
the glycerol into glucose. This is also a form of gluconeogenesis.
Taken together, these actions increase blood glucose levels. The activity of glucagon is regulated through a
negative feedback mechanism; rising blood glucose levels inhibit further glucagon production and
secretion.

Homeostatic Regulation of Blood Glucose

Levels: Blood glucose concentration is
tightly maintained between 70 mg/dL and
110 mg/dL. If blood glucose concentration
rises above this range, insulin is released,
which stimulates body cells to remove
glucose from the blood. If blood glucose
concentration drops below this range,
glucagon is released, which stimulates body
cells to release glucose into the blood.
Insulin
Insulin's principal purpose is to facilitate glucose uptake into bodily cells. Red blood cells, as well as brain,
liver, kidney, and small intestinal lining cells, lack insulin receptors on their cell membranes and hence do
not require insulin for glucose uptake. Although all other body cells require insulin to receive glucose from
the bloodstream, insulin's principal targets are skeletal muscle cells and fat cells. The release of
gastrointestinal tract hormones such as glucose-dependent insulinotropic peptides is triggered by the
presence of food in the intestine (previously known as a gastric inhibitory peptide). The beta cells of the
pancreas use this as a starting point for insulin generation and secretion. The increase in blood glucose
levels that happens as a result of dietary absorption promotes insulin secretion even more. It's not apparent
how insulin facilitates glucose uptake. Insulin, on the other hand, appears to activate a tyrosine kinase
receptor, causing phosphorylation of a variety of substrates within the cell. The migration of intracellular
vesicles containing facilitative glucose transporters to the cell membrane is aided by these various
metabolic processes. These transport proteins are ordinarily recycled slowly between the cell membrane
and the cell interior in the absence of insulin. Insulin causes a swarm of glucose transporter vesicles to rush
to the cell membrane, fusing and exposing the glucose transporters to the extracellular fluid. The
transporters then proceed to move glucose by facilitated diffusion into the cell interior.
Insulin also lowers blood glucose levels by promoting glycolysis, or glucose metabolism for the production
of ATP. It also encourages the liver to convert excess glucose into glycogen for storage and inhibits
glycogenolysis and gluconeogenesis enzymes. Finally, insulin stimulates the synthesis of triglycerides and
proteins. Insulin secretion is controlled by a negative feedback mechanism. Further insulin release is
inhibited as blood glucose levels fall.

Hormones of the Pancreas

Associated hormones Chemical class Effect

Insulin (beta cells) Protein Reduces blood glucose levels

Glucagon (alpha cells) Protein Increases blood glucose levels

Somatostatin (delta cells) Protein Inhibits insulin and glucagon release

Pancreatic polypeptide (PP cells) Protein Role in appetite

IN DISEASE
Diabetes Mellitus
Dysfunction of insulin production and secretion, as well as the target cells’ responsiveness to insulin, can
lead to a condition called diabetes mellitus.
There are two main forms of diabetes mellitus: Type 1 diabetes is an autoimmune disease affecting the
beta cells of the pancreas. Certain genes are recognized to increase susceptibility. The beta cells of people
with type 1 diabetes do not produce insulin; thus, synthetic insulin must be administered by injection or
infusion. This form of diabetes accounts for less than five percent of all diabetes cases. Type 2 diabetes
accounts for almost 95% of all diabetes cases. A person's risk is considerably increased by factors such as
family history, ethnicity, age, and the existence of pre-diabetes. Type 2 diabetes patients are frequently
overweight or obese, yet this is not the only risk factor. Type 2 diabetes causes cells to become resistant to
insulin's effects. The pancreas responds by increasing insulin output, but the beta cells eventually grow
tired. Type 2 diabetes can often be reversed with moderate weight loss, regular physical activity, and a
nutritious diet; but, if blood glucose levels cannot be controlled, the type 2 diabetic may require synthetic
insulin injections.
Excessive urination and excessive thirst are two of the first indications of diabetes. These signs and
symptoms show how high blood glucose levels have an impact on kidney function. The kidneys are in
charge of blood filtering. Excessive blood glucose causes water to be drawn into the urine, resulting in an
unusually large amount of urine being excreted. The use of bodily water to dilute urine dehydrates the
body, causing the person to be extremely thirsty and persistently thirsty. Because the bodily cells are
unable to access the glucose in the bloodstream, the person may sense continuous hunger.
Persistently high blood glucose levels harm tissues throughout the body, particularly those of the blood
vessels and nerves, over time. Atherosclerosis is caused by inflammation and irritation to the artery lining,
which increases the risk of heart attack and stroke. Kidney function is harmed by damage to the renal's
microscopic blood vessels, which can lead to kidney failure. Damage to the retina's blood vessels can
result in blindness. Blood vessel damage also lowers circulation to the limbs, whereas nerve injury causes
neuropathy, which causes a loss of sensation, especially in the hands and feet. These alterations together
raise the risk of injury, infection, and tissue death (necrosis), contributing to a high rate of toe, foot, and
lower-limb amputation among diabetics. A ketoacidosis is a serious form of metabolic acidosis caused by
uncontrolled diabetes. When cells are deprived of glucose, they begin to rely on fat energy stores. In a
glucose-deficient state, however, the liver is compelled to employ an alternate lipid metabolism pathway,
which leads to an increase in the generation of acidic ketone bodies (or ketones). Ketoacidosis is caused
by a build-up of ketones in the blood, which can progress to a life-threatening "diabetes coma" if left
untreated.
When blood glucose levels are greater than usual, a condition known as hyperglycemia, diabetes is
diagnosed. Diabetes therapy is determined by the type of diabetes, the severity of the condition, and the
patient's capacity to make lifestyle adjustments. As previously said, type 2 diabetics can lower their blood
glucose levels by losing weight, exercising regularly, and eating a healthy diet. Some patients with type 2
diabetes may require medication if they are unable to control their disease with these lifestyle changes.
Insulin was once the first-line treatment for type 2 diabetes. Alternative solutions, including drugs that
improve pancreatic function, have emerged as a result of research discoveries.
References:
Biga, L. M. (n.d.). 17.9 The Pancreas – Anatomy & Physiology. Pressbooks. Retrieved October 11, 2021,
from https://open.oregonstate.education/aandp/chapter/17-9-the-pancreas/#tbl-ch18_07
B. (n.d.). The Pancreas | Boundless Anatomy and Physiology. Lumen. Retrieved October 11, 2021, from
https://courses.lumenlearning.com/boundless-ap/chapter/the-pancreas/