Hormones of the Pancreas
The bulk of the pancreas is an exocrine gland secreting pancreatic fluid into the duodenum after a meal. (Discussion)
However, scattered through the pancreas are several hundred thousand clusters of cells called islets of Langerhans. The islets are endocrine tissue containing four types of cells. In order of abundance, they are the:
- beta cells, which secrete insulin
- alpha cells, which secrete glucagon
- delta cells, which secrete somatostatin, and
- gamma cells, which secrete a polypeptide of unknown function
Beta Cells
The beta cells of the islets secrete insulin. Insulin is a small protein consisting of- an alpha chain of 21 amino acids linked by two disulfide (S-S) bridges to a
- beta chain of 30 amino acids.
Beta cells have channels in their plasma membrane that serve as glucose detectors. Beta cells secrete insulin in response to a rising level of circulating glucose ("blood sugar").
Insulin affects many organs.
- Insulin stimulates liver cells to take up glucose from the blood and convert it into glycogen.
- Insulin stimulates skeletal muscle fibers to
- take up amino acids from the blood and convert them into protein
- take up glucose and convert it into glycogen
- Insulin acts on fat (adipose) cells to stimulate the synthesis of fat.
Taken together, all of these actions result in:
- the storage of the soluble nutrients absorbed from the intestine into insoluble, energy-rich products (glycogen, protein, fat)
- a drop in the level of blood sugar
Diabetes Mellitus
Diabetes mellitus is an endocrine disorder characterized by many signs and symptoms. Primary among these are:
- a failure of the kidney to reclaim glucose so that glucose spills over into the urine
- a resulting increase in the volume of urine because of the osmotic effect of this glucose (it reduces the return of water to the blood).
| Diabetes mellitus is a disorder quite distinct from the similarly-named diabetes insipidus. They both result in the production of large amounts of urine (diabetes), but in one the urine is sweet while in the other (caused by ADH deficiency) it is not. Before the days of laboratory tests, a simple taste test ("mellitus" or "insipidus") enabled the doctor to make the correct diagnosis. |
There are two forms of diabetes mellitus:
- Insulin-Dependent Diabetes Mellitus (IDDM) [also called "Type 1" diabetes] and
- Non Insulin-Dependent Diabetes Mellitus (NIDDM)["Type 2"]
Insulin-Dependent Diabetes Mellitus (IDDM)
IDDM (also called Type 1 diabetes)
- is characterized by little (hypo) or no circulating insulin
- most commonly appears in childhood
- it results from destruction of the beta cells of the islets
- the destruction results from an autoimmune attacks against the beta cells
- what triggers this attack is still a mystery, although a prior viral infection may be the culprit.
IDDM is controlled by carefully-regulated injections of insulin. (Insulin cannot be taken by mouth because, being a protein, it would be digested.)
For many years, insulin extracted from the glands of cows and pigs was used. However, pig insulin differs from human insulin by one amino acid; beef insulin by three. Although both work in humans to lower blood sugar, they are seen by the immune system as "foreign" and induce an antibody response in the patient that blunts their effect and requires higher doses.
Two approaches have been taken to solve this problem:
- Convert pig insulin into human insulin by removing the one amino acid that distinguishes them and replacing it with the human version. This approach is expensive, so now the favored approach is to
- Insert the human gene for insulin into E. coli and grow recombinant human insulin in culture tanks. Insulin is not a glycoprotein so E. coli is able to manufacture a fully-functional molecule (trade name = Humulin). Yeast is also used (trade name = Novolin).
Injections of insulin must be done carefully. Injections after vigorous exercise or long after a meal may drive the blood sugar level down to a dangerously low value causing an insulin reaction. The patient becomes irritable, fatigued, and may lose consciousness. If the patient is still conscious, giving a source of sugar (e.g., candy) by mouth usually solves the problem quickly. Injections of glucagon are sometimes used.
Many people develop diabetes mellitus without an accompanying drop in insulin levels (at least at first).
Their problem appears to be a failure to express a sufficient number of glucose transporters in the plasma membrane (and T-system) of their skeletal muscles.
Normally when insulin binds to its receptor on the cell surface, it initiates a chain of events that leads to the insertion in the plasma membrane of increased numbers of a transmembrane glucose transporter.
This transporter forms a channel that permits the facilitated diffusion of glucose into the cell.
Skeletal muscle is the major "sink" for removing excess glucose from the blood (and converting it into glycogen). In NIDDM, the patient's ability to remove glucose from the blood and convert it into glycogen may be only 20% of normal. Curiously, vigorous exercise seems to increase the expression of the glucose transporter (called GLUT-4) on skeletal muscle and this may explain why IDDM is more common in people who live sedentary lives.
NIDDM (also called Type 2 diabetes mellitus) usually strikes in adults and, particularly often, in overweight people. However, over the last few years in the U. S., the incidence of NIDDM in children has grown to the point where they now account for 20% of all newly-diagnosed cases.
Several drugs, all of which can be taken by mouth, are useful in restoring better control over blood sugar in patients with NIDDM.
The alpha cells of the islets secrete glucagon, a polypeptide of 29 amino acids.
Glucagon acts principally on the liver where it stimulates the conversion of glycogen into glucose which is deposited in the blood.
Glucagon secretion is
- stimulated by low levels of glucose in the blood and
- inhibited by high levels.
The physiological significance of this is that glucagon functions to maintain a steady level of blood sugar level between meals.
Injections of glucagon are sometimes given to diabetics suffering from an insulin reaction in order to speed the return of normal levels of blood sugar.
The delta cells secrete somatostatin. This consists of two polypeptides, one of 14 amino acids (the most active) and one of 28.
Somatostatin has a variety of functions. Taken together, they work to reduce the rate at which food is absorbed from the contents of the intestine.
Somatostatin is also secreted by the hypothalamus and by the stomach. Further information about somatostatin can be found by following these links.
Gamma Cells
The gamma cells of the islets secrete pancreatic polypeptide. No function has yet been found for this peptide of 36 amino acids.
24 July 1999
