Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 21

Endocrine Functions of the Pancreas & Regulation of Carbohydrate Metabolism 317

in heterologous species but are sufficient to make the insulin

antigenic. If insulin of one species is injected for a prolonged

period into another species, the anti-insulin antibodies

formed inhibit the injected insulin. Almost all humans who

have received commercial bovine insulin for more than 2 mo

have antibodies against bovine insulin, but the titer is usually

low. Porcine insulin differs from human insulin by only one

amino acid residue and has low antigenicity. Human insulin

produced in bacteria by recombinant DNA technology is now

widely used to avoid antibody formation.

BIOSYNTHESIS & SECRETION

Insulin is synthesized in the rough endoplasmic reticulum of

the B cells (Figure 21–3). It is then transported to the Golgi ap-

paratus, where it is packaged into membrane-bound granules.

These granules move to the plasma membrane by a process in-

volving microtubules, and their contents are expelled by exo-

cytosis (see Chapter 2). The insulin then crosses the basal

lamina of the B cell and a neighboring capillary and the fenes-

trated endothelium of the capillary to reach the bloodstream.

The fenestrations are discussed in detail in Chapter 32.

Like other polypeptide hormones and related proteins that

enter the endoplasmic reticulum, insulin is synthesized as

part of a larger preprohormone (see Chapter 1). The gene for

insulin is located on the short arm of chromosome 11 in

humans. It has two introns and three exons.

Preproinsulin

FIGURE 21–3
A and B cells, showing their relation to blood
vessels.
RER, rough endoplasmic reticulum. Insulin from the B cell and
glucagon from the A cell are secreted by exocytosis and cross the basal
lamina of the cell and the basal lamina of the capillary before entering
the lumen of the fenestrated capillary.
(Reproduced with permission from
Junqueira IC, Carneiro J:
Basic Histology: Text and Atlas,
10th ed. McGraw-Hill, 2003.)

Basal laminae

Fenestrations

Capillary

A cell

B cell

RER

Desmosome

Golgi

TABLE 21–1
Structure of human insulin (molecular weight 5808) and (below) variations in this structure in other
mammalian species.
a

Variations from Human Amino Acid Sequence

Species A Chain Position 8 9 10 B Chain Position 30

Pig, dog, sperm whale Thr-Ser-Ile Ala

Rabbit Thr-Ser-Ile Ser

Cattle, goat Ala-Ser-Val Ala

Sheep Ala-Gly-Val Ala

Horse Thr-Gly-Ile Ala

Sei whale Ala-Ser-Thr Ala

a
In the rat, the islet cells secrete two slightly different insulins, and in certain fish four different chains are found.

A chain

Gly-Ile-Val-Glu-Gin-Cys-Cys-Thr-Ser-Ile-Cys-Ser-Leu-Tyr-Gin-Leu-Glu-Asn-Tyr-Cys-Asn

1 2345 6

S

S

S

S

S

S

8910 11 1 2 13 14 15 16 17 18 1921

B chain

Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val-Cys-Gly-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Thr

1 2345 6 7 8910 11 1 2 13 14 15 1617 18 1921 20 22 23 24 2 5 26 2 7 28 29 30