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Hormones of the Pancreas

Index to this page

a.. Beta Cells

b.. Diabetes Mellitus

a.. Type 1 (IDDM)

b.. Type 2 (NIDDM)

c.. Inherited Forms of Diabetes Mellitus

c.. Alpha Cells

d.. Delta Cells

e.. Gamma Cells

The bulk of the pancreas is an exocrine gland secreting pancreatic fluid into

the duodenum after a meal. (Discussion) Link to graphic showing the location

of the pancreas and other endocrine

glands (92K).

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:

a.. beta cells, which secrete insulin

b.. alpha cells, which secrete glucagon

c.. delta cells, which secrete somatostatin, and

d.. 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

a.. an alpha chain of 21 amino acids linked by two disulfide (S-S) bridges to

a

b.. 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.

a.. Insulin stimulates liver cells to take up glucose from the blood and

convert it into glycogen.

b.. Insulin stimulates skeletal muscle fibers to

a.. take up amino acids from the blood and convert them into protein

b.. take up glucose and convert it into glycogen

c.. Insulin acts on fat (adipose) cells to stimulate the synthesis of fat.

In each case, insulin triggers these effects by binding to the insulin receptor

- a transmembrane protein embedded in the plasma membrane of the responding

cells.

Taken together, all of these actions result in:

a.. the storage of the soluble nutrients absorbed from the intestine into

insoluble, energy-rich products (glycogen, protein, fat)

b.. 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.. a failure of the kidney to reclaim glucose so that glucose spills over

into the urine

b.. 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 three categories of diabetes mellitus:

a.. Insulin-Dependent Diabetes Mellitus (IDDM) [also called " Type 1 " diabetes]

and

b.. Non Insulin-Dependent Diabetes Mellitus (NIDDM)[ " Type 2 " ]

c.. Inherited Forms of Diabetes Mellitus

Insulin-Dependent Diabetes Mellitus (IDDM)

IDDM (also called Type 1 diabetes)

a.. is characterized by little (hypo) or no circulating insulin;

b.. most commonly appears in childhood.

c.. It results from destruction of the beta cells of the islets.

d.. The destruction results from a cell-mediated autoimmune attack against the

beta cells.

e.. 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:

a.. 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

b.. 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.

Non Insulin-Dependent Diabetes Mellitus (NIDDM)

Many people develop diabetes mellitus without an accompanying drop in insulin

levels (at least at first).

In many cases, the 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. Discussion of how transmembrane

proteins are moved to the surface of the cell in which they are synthesized.

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 (and, like their adult

counterparts, are usually overweight).

Several drugs, all of which can be taken by mouth, are useful in restoring

better control over blood sugar in patients with NIDDM.

Inherited Forms of Diabetes Mellitus

Some cases of diabetes result from mutant genes inherited from one or both

parents. Examples:

a.. mutant genes for one or another of the transcription factors needed for

transcription of the insulin gene (5 mutant versions have been identified).

b.. mutations in one or both copies of the gene encoding the insulin receptor.

These patients usually have extra-high levels of circulating insulin but

defective receptors. The mutant receptors

a.. may fail to be expressed properly at the cell surface or

b.. may fail to transmit an effective signal to the interior of the cell.

c.. a mutant version of the gene encoding glucokinase, the enzyme that

phosphorylates glucose in the first step of glycolysis;

While symptoms usually appear in childhood or adolescence, patients with

inherited diabetes differ from most children with NIDDM in

a.. having a history of diabetes in the family and

b.. not being obese.

Alpha Cells

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

a.. stimulated by low levels of glucose in the blood and

b.. 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.

Delta Cells

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.

Mark E. Armstrong

www.top5plus5.com

Oregon State Chapter Rep

Pancreatitis Association, International