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15.9: Endocrine Pancreas

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  • By the end of this section, you will be able to:

    • Describe the location and structure of the pancreas, and the morphology and function of the pancreatic islets
    • Compare and contrast the functions of insulin and glucagon

    The pancreas is a long, slender retroperitoneal organ, most of which is located posterior to the bottom half of the stomach (Figure \(\PageIndex{1}\)). It is bordered on its right by the retroperitoneal section of the duodenum and on its left by the spleen. The acinar cells of the pancreas line many short cul-de-sac-shaped areas connected directly to the pancreatic duct that drains transversely through the core of the pancreas to the duodenum nestled against its right side. Although it is primarily an exocrine gland, with its acinar cells secreting a variety of digestive enzymes that comprise pancreatic juice that will function outside the epithelial lining of the small intestine, the pancreas also has an endocrine function. Scattered around the cul-de-sacs of acinar cells throughout the pancreas are about a million pancreatic islets—clusters of cells formerly known as the islets of Langerhans— that secrete the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide (PP).

    Diagram of pancreas alongside a micrograph showing the exocrine acinar cells connected to branches of the pancreatic duct and endocrine pancreatic islets.
    Figure \(\PageIndex{1}\): The Pancreas. (a) The taller head of the pancreas is attached to the left surface of the duodenum of the small intestine, just inferior to the stomach. The thinner tail of the pancreas extends across the midline toward the spleen. The pancreas consists of many functional lobules. Within a pancreatic lobule are two functional areas: Acinar cells have an exocrine function to secrete digestive enzymes into the pancreatic duct at the center of the organ in which pancreatic juice travels to the duodenum just after the duct merges with the common bile duct. Pancreatic islets are not connected to the pancreatic duct and have an endocrine function; alpha and beta cells of the islets secrete pancreatic hormones into the bloodstream. (b) A lighter-staining pancreatic islet is shown at the center of this micrograph surrounded by darker-staining acinar cells. LM X 200. (Image credit: "Exocrine and Endocrine Pancreas" by Julie Jenks is licensed under CC BY 4.0 / A derivative from the original work in (a) and the original work in (b))

    Cells and Secretions of the Pancreatic Islets

    Each pancreatic islet contains four types of cells whose secretions move into the bloodstream to travel to their target cells:

    • The alpha cell produces the hormone glucagon and makes up approximately 20 percent of each islet. Glucagon plays an important role in blood glucose regulation; low blood glucose levels stimulate its release.
    • The beta cell produces the hormone insulin and makes up approximately 75 percent of each islet. Elevated blood glucose levels stimulate the release of insulin.
    • The delta cell accounts for four percent of the islet cells and secretes the peptide hormone somatostatin. Recall that somatostatin is also released by the hypothalamus (as GHIH), and the stomach and intestines also secrete it. An inhibiting hormone, pancreatic somatostatin inhibits the release of both glucagon and insulin.
    • The PP cell accounts for about one percent of islet cells and secretes the pancreatic polypeptide hormone. It is thought to play a role in appetite, as well as in the regulation of pancreatic exocrine and endocrine secretions. Pancreatic polypeptide released following a meal may reduce further food consumption; however, it is also released in response to fasting.

    Regulation of Blood Glucose Levels by Insulin and Glucagon

    Glucose is required for cellular respiration and is the preferred fuel for all body cells. The body derives glucose from the breakdown of the carbohydrate-containing foods and drinks we consume. Glucose not immediately taken up by cells for fuel can be stored by the liver and muscles as glycogen, or converted to triglycerides and stored in the adipose tissue. Hormones regulate both the storage and the utilization of glucose as required. Receptors located in the pancreas sense blood glucose levels, and subsequently the pancreatic cells secrete glucagon or insulin to maintain normal levels.


    Receptors in the pancreas can sense the decline in blood glucose levels, such as during periods of fasting or during prolonged labor or exercise (Figure \(\PageIndex{2}\)). In response, the alpha cells of the pancreas secrete the hormone glucagon, which has several effects:

    • It 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 body cells.
    • It stimulates the liver to take up amino acids from the blood and convert them into glucose. This response is known as gluconeogenesis.
    • It 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 it 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.


    The primary function of insulin is to facilitate the uptake of glucose into body cells. Red blood cells, as well as cells of the brain, liver, kidneys, and the lining of the small intestine, do not have insulin receptors on their cell membranes and do not require insulin for glucose uptake. Although all other body cells do require insulin if they are to take glucose from the bloodstream, skeletal muscle cells and adipose cells are the primary targets of insulin.

    The presence of food in the intestine leads to insulin production and secretion by the beta cells of the pancreas. Once nutrient absorption occurs, the resulting surge in blood glucose levels further stimulates insulin secretion.


    Pancreas Location and Endocrine Function

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    Watch this video describing the location and endocrine function of the pancreas. What goes wrong in the function of insulin in type 2 diabetes?


    Answer: Insulin is overproduced after cells become resistant to insulin's effect.

    Insulin also reduces blood glucose levels by stimulating glycolysis, the metabolism of glucose for generation of ATP. Moreover, it stimulates the liver to convert excess glucose into glycogen for storage, and it inhibits enzymes involved in glycogenolysis and gluconeogenesis because the body doesn't need to free more glucose. Finally, insulin promotes triglyceride and protein synthesis. The secretion of insulin is regulated through a negative feedback mechanism. As blood glucose levels decrease, further insulin release is inhibited. The pancreatic hormones are summarized in Table \(\PageIndex{1}\).

    Table \(\PageIndex{1}\): Hormones of the Pancreas
    Associated hormone (and the cells that secretes it) Effect
    Insulin (beta cells) Reduces blood glucose levels
    Glucagon (alpha cells) Increases blood glucose levels
    Somatostatin (delta cells) Inhibits insulin and glucagon release


    Endocrine System: 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. An increasingly common disease, diabetes mellitus has been diagnosed in more than 18 million adults in the United States, and more than 200,000 children. It is estimated that up to 7 million more adults have the condition but have not been diagnosed. In addition, approximately 79 million people in the US are estimated to have pre-diabetes, a condition in which blood glucose levels are abnormally high, but not yet high enough to be classified as diabetes.

    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 approximately 95 percent of all cases. It is acquired, and lifestyle factors such as poor diet, inactivity, and the presence of pre-diabetes greatly increase a person’s risk. About 80 to 90 percent of people with type 2 diabetes are overweight or obese. In type 2 diabetes, cells become resistant to the effects of insulin. In response, the pancreas increases its insulin secretion, but over time, the beta cells become exhausted. In many cases, type 2 diabetes can be reversed by moderate weight loss, regular physical activity, and consumption of a healthy diet; however, if blood glucose levels cannot be controlled, the diabetic will eventually require insulin.

    Two of the early manifestations of diabetes are excessive urination and excessive thirst. They demonstrate how the out-of-control levels of glucose in the blood affect kidney function. The kidneys are responsible for filtering glucose from the blood. Excessive blood glucose draws water into the urine, and as a result the person eliminates an abnormally large quantity of sweet urine. The use of body water to dilute the urine leaves the body dehydrated, and so the person is unusually and continually thirsty. The person may also experience persistent hunger because the body cells are unable to access the glucose in the bloodstream.

    Over time, persistently high levels of glucose in the blood injure tissues throughout the body, especially those of the blood vessels and nerves. Inflammation and injury of the lining of arteries lead to atherosclerosis and an increased risk of heart attack and stroke. Damage to the microscopic blood vessels of the kidney impairs kidney function and can lead to kidney failure. Damage to blood vessels that serve the eyes can lead to blindness. Blood vessel damage also reduces circulation to the limbs, whereas nerve damage leads to a loss of sensation, called neuropathy, particularly in the hands and feet. Together, these changes increase the risk of injury, infection, and tissue death (necrosis), contributing to a high rate of toe, foot, and lower leg amputations in people with diabetes. Uncontrolled diabetes can also lead to a dangerous form of metabolic acidosis called ketoacidosis. Deprived of glucose, cells increasingly rely on fat stores for fuel. However, in a glucose-deficient state, the liver is forced to use an alternative lipid metabolism pathway that results in the increased production of ketone bodies (or ketones), which are acidic. The build-up of ketones in the blood causes ketoacidosis, which—if left untreated—may lead to a life-threatening “diabetic coma.” Together, these complications make diabetes the seventh leading cause of death in the United States.

    Diabetes is diagnosed when lab tests reveal that blood glucose levels are higher than normal, a condition called hyperglycemia. The treatment of diabetes depends on the type, the severity of the condition, and the ability of the patient to make lifestyle changes. As noted earlier, moderate weight loss, regular physical activity, and consumption of a healthful diet can reduce blood glucose levels. Some patients with type 2 diabetes may be unable to control their disease with these lifestyle changes, and will require medication. Historically, the first-line treatment of type 2 diabetes was insulin. Research advances have resulted in alternative options, including medications that enhance pancreatic function.

    Concept Review

    The pancreas has both exocrine and endocrine functions. The pancreatic islet cell types include alpha cells, which produce glucagon; beta cells, which produce insulin; delta cells, which produce somatostatin; and PP cells, which produce pancreatic polypeptide. Insulin and glucagon are involved in the regulation of glucose metabolism. Insulin is produced by the beta cells in response to high blood glucose levels. It enhances glucose uptake and utilization by target cells, as well as the storage of excess glucose for later use. Dysfunction of the production of insulin or target cell resistance to the effects of insulin causes diabetes mellitus, a disorder characterized by high blood glucose levels. The hormone glucagon is produced and secreted by the alpha cells of the pancreas in response to low blood glucose levels. Glucagon stimulates mechanisms that increase blood glucose levels, such as the catabolism of glycogen into glucose.

    Review Questions

    Q. If an autoimmune disorder targets the alpha cells, production of which hormone would be directly affected?

    A. somatostatin

    B. pancreatic polypeptide

    C. insulin

    D. glucagon


    Answer: D

    Q. Which of the following statements about insulin is true?

    A. Insulin acts as a transport protein, carrying glucose across the cell membrane.

    B. Insulin facilitates the movement of intracellular glucose transporters to the cell membrane.

    C. Insulin stimulates the breakdown of stored glycogen into glucose.

    D. Insulin stimulates the kidneys to reabsorb glucose into the bloodstream.


    Answer: B

    Critical Thinking Questions

    Q. Compare and contrast the anatomy related to the exocrine and endocrine functions of the pancreas.


    A. The pancreas produces a variety of secretions that leave the pancreas to function in other organs of the body. The destination of the secretion defines whether it is part of the exocrine or endocrine function of the pancreas. The acinar cells of the pancreas produce and secrete digestive enzymes. The acinar cells are arranged in cul-de-sacs connected to the pancreatic duct, through which the digestive enzymes are delivered to the duodenum of the small intestine. They are considered exocrine in nature because they will pass through the epithelial lining of the small intestine in the opposite direction of nutrient absorption to mix with and chemically digest intestinal contents. Pancreatic islets are scattered throughout the remainder of the pancreas and contain four types of endocrine cells whose secretions enter the bloodstream to travel to their target organs. Alpha cells secrete glucagon which causes an increase in blood sugar by stimulating the liver to release glucose into the bloodstream. Beta cells secrete insulin which signals cells to take in glucose, thereby reducing blood sugar levels. Delta cells secrete somatostatin, which inhibits the release of both glucagon and insulin. PP cells secrete the pancreatic polypeptide hormone that regulates appetite as well as both exocrine and endocrine functions of the pancreas.


    alpha cell
    pancreatic islet cell type that produces the hormone glucagon
    beta cell
    pancreatic islet cell type that produces the hormone insulin
    delta cell
    minor cell type in the pancreas that secretes the hormone somatostatin
    diabetes mellitus
    condition caused by destruction or dysfunction of the beta cells of the pancreas or cellular resistance to insulin that results in abnormally high blood glucose levels
    pancreatic hormone that stimulates the catabolism of glycogen to glucose, thereby increasing blood glucose levels
    abnormally high blood glucose levels
    pancreatic hormone that enhances the cellular uptake and utilization of glucose, thereby decreasing blood glucose levels
    organ with both exocrine and endocrine functions located posterior to the stomach that is important for digestion and the regulation of blood glucose
    pancreatic islets
    specialized clusters of pancreatic cells that have endocrine functions; also called islets of Langerhans
    PP cell
    minor cell type in the pancreas that secretes the hormone pancreatic polypeptide

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