Ganong's Review of Medical Physiology, 23rd Edition

446 SECTION V Gastrointestinal Physiology

both gastrointestinal hormones is increased by a protein meal,
either or both may be the “gut factor” that stimulates glucagon
secretion (see Chapter 21). Two CCK receptors have been
identified. CCK-A receptors are primarily located in the
periphery, whereas both CCK-A and CCK-B receptors are
found in the brain. Both activate PLC, causing increased pro-
duction of IP 3 and DAG (see Chapter 2).
The secretion of CCK is increased by contact of the intesti-
nal mucosa with the products of digestion, particularly pep-
tides and amino acids, and also by the presence in the
duodenum of fatty acids containing more than 10 carbon
atoms. There are also two protein releasing factors that acti-
vate CCK secretion, known as CCK-releasing peptide and
monitor peptide, which derive from the intestinal mucosa and
pancreas, respectively. Because the bile and pancreatic juice
that enter the duodenum in response to CCK further the
digestion of protein and fat, and the products of this digestion
stimulate further CCK secretion, a sort of positive feedback
operates in the control of the secretion of this hormone. How-
ever, the positive feedback is terminated when the products of
digestion move on to the lower portions of the gastrointesti-
nal tract, and also because CCK-releasing peptide and moni-
tor peptide are degraded by proteolytic enzymes once these
are no longer occupied in digesting dietary proteins.

SECRETIN

Secretin occupies a unique position in the history of physiolo-
gy. In 1902, Bayliss and Starling first demonstrated that the ex-
citatory effect of duodenal stimulation on pancreatic secretion
was due to a bloodborne factor. Their research led to the iden-
tification of the first hormone, secretin. They also suggested
that many chemical agents might be secreted by cells in the
body and pass in the circulation to affect organs some distance
away. Starling introduced the term hormone to categorize
such “chemical messengers.” Modern endocrinology is the
proof of the correctness of this hypothesis.
Secretin is secreted by S cells that are located deep in the
glands of the mucosa of the upper portion of the small intes-
tine. The structure of secretin (Table 26–6) is different from
that of CCK and gastrin, but very similar to that of glucagon,
GLI, VIP, and GIP. Only one form of secretin has been iso-
lated, and the fragments of the molecule that have been tested
to date are inactive. Its half-life is about 5 minutes, but little is
known about its metabolism.
Secretin increases the secretion of bicarbonate by the duct
cells of the pancreas and biliary tract. It thus causes the secre-
tion of a watery, alkaline pancreatic juice. Its action on pan-
creatic duct cells is mediated via cAMP. It also augments the
action of CCK in producing pancreatic secretion of digestive
enzymes. It decreases gastric acid secretion and may cause
contraction of the pyloric sphincter.
The secretion of secretin is increased by the products of pro-
tein digestion and by acid bathing the mucosa of the upper
small intestine. The release of secretin by acid is another exam-

ple of feedback control: Secretin causes alkaline pancreatic juice

to flood into the duodenum, neutralizing the acid from the

stomach and thus inhibiting further secretion of the hormone.

GIP

GIP contains 42 amino acid residues (Table 26–6) and is pro-

duced by K cells in the mucosa of the duodenum and jejunum.

Its secretion is stimulated by glucose and fat in the duodenum,

and because in large doses it inhibits gastric secretion and mo-

tility, it was named gastric inhibitory peptide. However, it now

appears that it does not have significant gastric inhibiting ac-

tivity when administered in smaller amounts comparable to

those seen after a meal. In the meantime, it was found that GIP

stimulates insulin secretion. Gastrin, CCK, secretin, and glu-

cagon also have this effect, but GIP is the only one of these that

stimulates insulin secretion when administered in doses that

produce blood levels comparable to those produced by oral

glucose. For this reason, it is often called glucose-dependent

insulinotropic polypeptide. The glucagon derivative GLP-1

(7–36) (see Chapter 21) also stimulates insulin secretion and

is said to be more potent in this regard than GIP. Therefore, it

may also be a physiologic B cell-stimulating hormone of the

gastrointestinal tract.

The integrated action of gastrin, CCK, secretin, and GIP in

facilitating digestion and utilization of absorbed nutrients is

summarized in Figure 26–23.

FIGURE 26–23 Integrated action of gastrointestinal

hormones in regulating digestion and utilization of absorbed

nutrients. The dashed arrows indicate inhibition. The exact identity of

the hormonal factor or factors from the intestine that inhibit(s) gastric

acid secretion and motility is unsettled, but it may be peptide YY.

Food in stomach

Gastrin secretion

Increased

motility

Increased acid

secretion

Food and acid

into duodenum

CCK

and secretin

secretion

GIP

GLP-1 (7–26)

secretion

Insulin

Pancreatic and secretion

biliary secretion

Intestinal digestion

of food

Peptide YY?