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WORKBOOK 10
Irritable bowel syndrome, constipation,
and diarrhoea
Helen: a simplified case history
Helen finally decides to see her GP about the symptoms she has been experiencing for some
time, and which have become worse over the last few weeks. Part of the reason she has not
sought help earlier is that the symptoms are constantly changing, alternating between
constipation and diarrhoea. She also has other, more non-specific, symptoms that can be just
as irritating.
A table of clinical clerking abbreviations is given on page xviii.
CLINICAL CLERKING FOR HELEN JONES AT THE GP SURGERY
Age: 39 years.
Weight: 60 kg.
PC: Abdominal pain, constipation, recurrent heartburn, nausea.
HPC: Painful abdominal cramps, accompanied by bloating and rumblings have been recurrent for
9 months. Abdominal pain is more severe after eating and at night. Constipation is intermittent; she
sometimes suffers diarrhoea instead. Urgent need to defecate several times in the morning, including
during and after breakfast. Has also felt lethargic, and quite anxious.
PMH: Nil.
DH: Gaviscon®, senna, and loperamide occasionally as per pharmacist’s recommendations.
Her pharmacist has recommended the above drugs at different periods when she has requested
medication for heartburn, constipation, and diarrhoea, respectively.
SH: Lives with husband and two daughters. Currently under a lot of stress, working long hours, leading a
project with a tight deadline.
O/Q: Helen reveals that her urinary frequency has increased. She also feels depressed. The GP’s
questions reveal the following.
1) The pain of heartburn is relieved by defecation.
2) The abdominal pain is associated with a change of frequency and consistency of stools.
3) Frequency of bowel movements often varies from more than three motions per day to fewer than
three per week.
WORKBOOK 10 Irritable bowel syndrome, constipation, and diarrhoea 343
4) The stool form keeps altering from lumpy/hard to loose/watery.
5) The passage of stool alters from needing to strain, to urgency and a feeling of incomplete evacuation.
6) There is a lot of mucus present in her stools.
7) Her abdomen often feels distended (bloating).
She gives the following negative answers to the GP’s questions:
1) She has not lost weight.
2) She has not experienced gastrointestinal bleeding.
3) She is not anaemic.
4) She does not have an abdominal mass.
5) She does not have a family history of gastrointestinal malignancy, or inflammatory bowel
disease(IBD).
Unlike most other illnesses, irritable bowel syndrome (IBS) is a functional disorder; symptoms are
not explained by biochemical or structural abnormalities, and diagnosis is often difficult.
GPs tend to use the Rome criteria, which involves asking the patient about the above symptoms.
Alarm (red flag) symptoms that would prompt further investigations to exclude other diseases (e.g.
cancer and IBD) include:
•acuteorlateonset(age>50 years)
•weightloss
•gastrointestinalbleeding
•abdominalmassorfever,orsignsofinfection.
Helen does not have alarm symptoms.
In the presence of positive symptoms, and the absence of alarm symptoms, a diagnosis can be
made by the GP.
Diagnosis: Irritable bowel syndrome
The GP explains that Helen’s symptoms are consistent with IBS. He will prescribe some
medication; she should return in 2 months for a follow-up.
He mentions that some patients experience extra-colonic problems (e.g. lower backache,
nausea, gynaecological symptoms, and the increase in urinary frequency) and the feelings of
lethargy which Helen is suffering.
Helen has compared her symptoms with those of a work colleague who has ulcerative colitis.
She asks the GP if that is similar to IBS. The GP reassures her that it is not.
344 Chapter 13 Disorders of the lower gastrointestinal tract
Note: The treatment of IBS is unsatisfactory, and few new drugs have become available. Managing
the condition usually involves dietary modification to avoid triggers, together with some
pharmacological and dietary approaches. IBS is a condition for which some over-the-counter
products can be recommended. Community pharmacists should therefore be familiar with its
features, and be able to recognize red flag or alarm symptoms.
Plan:
• Commence peppermint oil capsules
• Commence mebeverine tablets
The GP explains that peppermint and mebeverine should help alleviate the symptoms of IBS,
but that Helen will need to be patient.
1a) Explain why IBS is considered a functional disorder.
1b) Explain the difference between IBS and IBD.
2) List the gastrointestinal and non-gastrointestinal symptoms of IBS, and their possible causes.
3a) What class of drugs are peppermint oil and mebeverine, and how do they act to relieve the
symptoms of IBS?
3b) Explain how mebeverine achieves smooth muscle relaxation.
4a) What is the second subclass of drugs that can be used to relax smooth muscle? Give two examples
of this type of drug.
4b) Explain how the drugs listed in your last answer act to relieve the symptoms of IBS.
5) What is thought to be the physiological basis of IBS?
A week later, Helen returns to the GP. She is feeling very down as a result of stress at work and
the IBS symptoms, which have not shown any improvement. After assessment, the GP decides
that she is suffering from clinical depression and prescribes imipramine.
Three weeks later, Helen is back at the GP’s surgery. Though she is no longer experiencing the
alternating diarrhoea and constipation, she is suffering with very bad constipation. She tells the
GP that she has less pain.
6) What is constipation?
7) What is the likely reason for Helen’s symptoms shifting to predominantly constipation? Explain your
reasoning.
8) What role does imipramine have in IBS therapy?
The GP prescribes sodium docusate to be taken twice a day, for 5 days only. The drug is
fast-acting and should rapidly relieve her constipation.
WORKBOOK 10 Irritable bowel syndrome, constipation, and diarrhoea 345
9) Describe the mechanism of action of docusate sodium.
The GP also asks Helen to keep a symptom diary, listing the foods she eats. This could help to
identify foods triggering the IBS. He advises her to drink a lot of water and to increase her
dietary fibre. Finally he prescribes a laxative called ispaghula husk (Fybogel®). She should take
one sachet twice a day for a week, and then use it as required.
10a) Ispaghula husk is an example of which type of laxative?
10b) Why would increasing fibre content of the diet be expected to relieve constipation?
10c) What are the risks associated with increasing fibre intake for an IBS sufferer?
The GP assures Helen that in the unlikely event that docusate and ispaghula are not effective,
other treatments for constipation are available.
11) What other options can be used to treat constipation? Give an example of each type, explain its
mode of action, and indicate whether it would be useful in the treatment of constipation dominant IBS.
Helen hopes the drugs will work because she wants to go to her friend Sunita’s wedding in Hawaii.
Her symptoms improve, and she makes it to the wedding.
As Helen helps Sunita prepare for her wedding she asks her about other treatments for IBS. Sunita
tells her that in the USA alosetron and prucalopride are prescribed to treat diarrhoea-dominant and
constipation-dominant IBS, respectively, in cases where other treatments have failed. Both these
drugs act at 5-HT (serotonin) receptors.
12) Describe the roles of 5-HT in the gut which make it a target for IBS therapy. (See Chapter 12,
Section 12.5.1)
13a) Which 5-HT receptors are targeted by alosetron and prucalopride? Are they agonists or
antagonists at these receptors?
13b) Why would targeting these receptors have differing effects on gastrointestinal tract motility?
14) Which group of medicines that act on the 5-HT uptake mechanism could be useful for treating
Helen’s condition, considering her medical history? Give three reasons why they would be suitable.
After the wedding, Helen and her family stay on for a holiday.
For the first couple of days Helen feels great. But on the third morning she is hardly able to
leave the bathroom. She thinks it might be something she has eaten, as this is the first IBS
symptom she has had since arriving in Hawaii.
15a) The definition of diarrhoea is subjective. What questions would you ask to determine if someone
has diarrhoea, and how would you expect them to answer if they do?
15b) What is the clinical definition of diarrhoea?
346 Chapter 13 Disorders of the lower gastrointestinal tract
15c) Describe the three main causes/types of diarrhoea.
16) List some of the causes of acute and chronic diarrhoea. Which is the most likely in Helen’s case?
Helen finds a pharmacy in the town centre. She explains her symptoms and the pharmacist
asks whether she has any known condition, or has started any medication recently, which may
explain the diarrhoea.
He sells her some oral rehydration sachets, and asks her to come back if the diarrhoea has not
improvedin3days.
17) What are the three main approaches in the treatment of acute diarrhoea?
18a) The pharmacist recommends an oral rehydration solution. Is that the right decision? Explain your
reasoning.
18b) What is the composition of World Health Organization oral rehydration solution?
18c) What is the rationale for this composition? How does the oral rehydration solution work?
A day later, although Helen has been taking the oral rehydration solution and drinking as
recommended, she still has diarrhoea and the abdominal cramps she experiences are very
painful. She returns to the pharmacy.
The pharmacist recommends loperamide and charcoal sachets.
19a) What type of drug is loperamide, and how might it improve the symptoms of diarrhoea?
19b) Codeine is another opiate used to slow the gut. Which is a better choice for the treatment of
diarrhoea: loperamide or codeine? Give reasons to support your choice.
20) Explain the rationale for using adsorbents such as charcoal in the treatment of diarrhoea. What is the
current role of these agents?
Helen’s symptoms improve 2 days later, which is timely because she will not have to worry
about diarrhoea on the long flight home.
Chapter 14
Diabetes mellitus and obesity
Useful terms for this topic
cells: Endocrine cells in the islets of Langerhans in
the pancreas, responsible for secreting insulin.
Glucagon: Hormone secreted by the -cells in the
pancreas in response to low blood glucose levels.
Gluconeogenesis: Synthesis of glucose from
non-carbohydrate sources.
Glycogen: Readily mobilizable storage form of
glucose.
Glycosuria: Appearance of glucose in the urine.
Hyperglycaemia: High levels of glucose in the blood.
Incretins: Short-lived hormones released from cells in
the gastrointestinal tract that promote release of
insulin by the pancreas.
Insulin: Hormone secreted by the -cells in the
pancreas in response to increased blood glucose
concentration. Principal hormone in regulation of
blood glucose levels.
Insulin resistance: Reduced sensitivity of tissues to
insulin.
Islets of Langerhans: Endocrine tissue in the
pancreas responsible for secretion of insulin and
glucagon.
Macrovascular damage: Long-term complication of
diabetes involving large blood vessels, such as the
coronary arteries, which show accelerated
atherosclerosis.
Metabolic syndrome: A cluster of disorders including
obesity, insulin resistance, hypertension, and
hyperlipidaemia. Often precedes type II diabetes.
In the previous two chapters we have considered
disorders aecting the function of the gastrointestinal
tract where food is digested and nutrients absorbed. Here
we consider diabetes, the most common disturbance of
intermediary metabolism—the chemical reactions
governing the conversion of nutrients into cellular
components. In diabetes the usual tight control of blood
glucose levels is lost due to a reduction in the eects of
the hormone insulin. e diabetic patient is at risk of
serious acute and long-term complications as a
consequence of high blood glucose levels
(hyperglycaemia). Conversely, treatment with
replacement insulin or some oral antidiabetic therapies
can put the patient at risk of glucose levels falling too far
(hypoglycaemia). Both hyperglycaemia and
hypoglycaemia can potentially result in the patient falling
into a coma, illustrating the need for good control over
blood glucose levels. Andreas, our ctional patient in
Workbook 11, is admitted to hospital with
hyperglycaemia and complications arising from
undiagnosed diabetes.
Obesity is also a metabolic disturbance in which the
mechanisms controlling energy balance are disordered.
Andreas is obese; his case highlights the link between
obesity and type II diabetes.
is chapter covers the pathophysiology and
management of both diabetes and obesity. We look into
the pathways that underlie the control of blood glucose
levels and the regulation of energy balance, in order to
appreciate how they can be modied by pharmacological
agents.
348 Chapter 14 Diabetes mellitus and obesity
14.1 Control of blood glucose levels
Despite the fact that our food intake is intermittent, blood
glucose levels must be maintained within a relatively
narrow range (usually between 4 and 6 mmol/l). is is
because the brain has an absolute dependency on
glucose as its source of fuel. Following ingestion of food,
excess energy-rich molecules are rapidly channelled into
stores, which can then be mobilized to cover the periods
between meals. Adequate circulating levels of glucose are
maintained by release of glucose from stores in the liver
(glycogen), and by its synthesis from non-carbohydrate
sources (gluconeogenesis). ese pathways must be
closely regulated in order to keep control over blood
glucose levels; the principal regulatory hormone is
insulin, released in response to increased blood glucose
levels. e eects of insulin are opposed by glucagon,
released when concentrations of glucose in the blood fall.
ese two hormones act in concert to keep tight control
on blood glucose levels.
14.1.1 Where is insulin synthesized?
Insulin is produced by the pancreas, a gland that lies
below and behind the stomach, across the back of the
abdomen (see Figure P4.1 in the Introduction to Part 4).
Only about 2% of the pancreas is endocrine (producing
hormones); the remainder is exocrine (producing
digestive enzymes; see Chapter 12). Within the pancreas,
the endocrine cells are arranged in small patches: the
islets of Langerhans. ere are a number of dierent cell
types within the islets:
• -cells are the most abundant; they secrete insulin,
and also amylin, a polypeptide that acts synergistically
with insulin
• -cells secrete the hormone glucagon, which opposes
the action of insulin (see Section 14.1.4)
• -cells (or D-cells) secrete somatostatin (see Chapter
12)
• PP-cells (or F-cells) secrete pancreatic polypeptide,
whose role is unclear. It may regulate the overall activity
of the pancreas, and is also believed to be involved in
regulating appetite and food intake.
14.1.2 Production of insulin
Insulin is a protein consisting of two amino acid chains, A
and B. e A chain contains 21 amino acids, while the B
chain contains 30. e two chains are linked by two
disulphide bridges. Insulin is synthesized in the
endoplasmic reticulum of the -cells as the precursor
preproinsulin. is is transported to the Golgi apparatus
where it is proteolytically cleaved to proinsulin. e
proinsulin is in turn cleaved to form insulin; the peptide
chain is hydrolysed at two points to give rise to the A and
B chains, linked by the disulphide bridges. e remaining
section of the precursor is termed C-peptide. is is
stored in granules in equimolar concentrations with
insulin, ready for release. A role for C-peptide is slowly
emerging. Until recently it was thought to be biologically
inactive, but it is now recognized that this molecule acts
at specic G-protein-coupled receptors to bring about
separate eects, closely related to those of insulin. It may
also act to stabilize both insulin and amylin, and to
maintain them in solution when they are released,
preventing precipitation which could damage the
pancreas. Once released, the half-life of C-peptide (20–50
minutes) is much longer than that of insulin (4–10
minutes), as it has a lower hepatic extraction ratio than
insulin, which is extensively metabolized in the liver. is
longer half-life makes C-peptide a clinically relevant
marker of insulin secretion; it is used diagnostically to
dierentiate between type I and type II diabetes (see
Section 14.2). e release of insulin from the pancreatic
-cells is stimulated by a rise in blood glucose levels. is
occurs after a carbohydrate-containing meal (postprandial), following the absorption of glucose in the small
intestine. e mechanism leading to insulin release is
illustrated in Box 14.1.
14.1.3 The actions of insulin
e eects of insulin on carbohydrate, fat, and protein
metabolism are mediated by activation of its cell surface
tyrosine kinase receptor. e receptor is a dimer,
stabilized by disulphide bridges, each half comprising an
and a subunit (see Chapter 2, Figure 2.15 and Section
2.2.5, for further description of the insulin receptor).
Stimulation of the receptor causes its
autophosphorylation, with one monomer
phosphorylating the other on the subunit, leading to
activation of its inbuilt tyrosine kinase. is enzyme
activity phosphorylates a large number of dierent
intracellular molecules, termed insulin-receptor
substrates (IRSs). When phosphorylated, these molecules
trigger signal transduction pathways, which bring about
the eects of insulin inside the cells. e main eects of
Box 14.1
Insulin release from -cells in the islets of Langerhans
+
+
K
+
+
–
Blood Vessel
2+
Ca
5
2+
Ca
+
Insulin +
C-peptide
Proinsulin
1
Preproinsulin
6
Incretins
e.g. GLP-1
Parasympathetic
nerves
Sympathetic
nerves
Glycolysis +
Krebs cycle
7
8
M
3
9
α
2
HO
OH
HO
3
Glucose
O
OH
OH
2
–
ATP
cAMP
2+
Ca
cAMP
Pancreatic
4
β cell
Figure a
1. Insulin is synthesized within pancreatic -cells by proteolytic cleavage of the
precursors preproinsulin and then proinsulin. It is stored in granules, together with
the peptide fragment C-peptide, awaiting release.
2. When its level in the blood reaches a critical concentration, glucose enters the
-cells from the bloodstream through GLUT-2, an insulin-independent membrane
glucose transporter.
3. Glucose is metabolized via glycolysis and the tricarboxylic acid cycle, to generate
ATP in the cell.
4. The increase in ATP causes ATP-sensitive K+ channels (K
membrane to close. In their open state leakage of K+ through these channels is the
main contributor to the resting potential across the membrane. The K
the site of action of the antidiabetic sulphonylureas and meglitinides.
5. The closing of the K
leads to the opening of voltage-gated Ca
6. The increase in intracellular Ca
exocytosis.
7. Release of insulin from -cells is influenced by a number of other inputs. Amongst
these are incretins: hormones from the gastrointestinal tract that potentiate insulin
release, but only in the presence of glucose. The main incretins are glucagon-like
peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Their
receptors are coupled through Gs to increases in cyclic AMP, which acts on a
distinct set of K+ channels. These channels are closed in response to cyclic AMP
levels rising, bringing about depolarization of the membrane, and hence insulin
release via the same exocytotic pathway. The -cell receptor for GLP-1 is the site of
action of the incretin mimetics.
channels causes depolarization of the membrane. This in turn
ATP
2 +
2 +
channels, and an influx of Ca
concentration triggers the release of insulin by
channels) in the -cell
ATP
channel is
ATP
2 +
.
Box 14.1 Insulin release from -cells in the islets of Langerhans
8. Innervation by the parasympathetic nervous system acting through Gq-coupled muscarinic M3 receptors leads to increases
in intracellular Ca
9. Insulin release is suppressed by the sympathetic nervous system, acting predominantly through 2 adrenoceptors coupled
to activation of K+ channels. These channels are distinct from those sensitive to sulphonylureas. When they open the
-cells becomes hyperpolarized and insulin secretion is inhibited.
ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; ⊖, inhibits; ⊕, promotes.
2 +
and promotes the release of insulin.
insulin are seen in the liver, adipose tissue, and skeletal
muscle. e mechanisms stimulated vary from one tissue
to the other, but the overall eects are those seen in the
absorptive state: increased storage of carbohydrate and
fats, and increased synthesis of proteins, as described
below and summarized in Table 14.1.
Effects on carbohydrate metabolism
of intracellular vesicles; insulin binding to its receptor
promotes the fusing of these vesicles and insertion of the
GLUT-4 proteins into the plasma membrane. is
promotes a rapid increase in glucose uptake from the
blood, thereby reducing the circulating level
(hypoglycaemic or glucose-lowering eect).
Following its facilitated passage via GLUT-4, glucose is
immediately phosphorylated to trap it inside the cells. As
Following ingestion of carbohydrates, the majority of
glucose uptake from the blood is accounted for by
insulin-stimulated transport into skeletal muscle and, to a
lesser extent, adipose tissue. Activation of the insulin
the mass of skeletal muscle in our bodies is so large,
insulin-controlled uptake of glucose into this tissue type
accounts for the majority (around 80%) of that ingested.
When the insulin receptor is no longer stimulated, the
receptor leads to the recruitment of specic insulindependent glucose transporters (GLUT-4), which are
especially abundant in these tissues. It is important to
note that adipose tissue and skeletal muscle are
completely reliant on GLUT-4 for glucose uptake. e
GLUT-4 transporter proteins are contained within a pool
In adipose tissue the insulin-stimulated uptake of glucose
is largely channelled into production of glycerol, a
building block in the synthesis of triglycerides, the storage
form of fats.
Table 14.1 The actions of insulin in target cells on carbohydrate, fat, and protein metabolism
Tissue Carbohydrate metabolism Fat metabolism Protein
metabolism
Liver cells
Adipose
tissue
Muscle
Gluconeogenesis
Glycogenesis (glycogen synthesis)
Glycogenolysis (breakdown of glycogen)
Glycolysis (metabolism of glucose to
pyruvate)
Glucose uptake
Glycerol synthesis (building block for
triglyceride synthesis)
Glucose uptake
Glycolysis
Glycogen synthesis
Glycogenolysis
Lipogenesis (simple sugars converted to fatty
acids)
Fatty acid breakdown (-oxidation)
Triglyceride synthesis from fatty acids and
glycerol
Fatty acid uptake
Lipolysis
Extracellular degradation of chylomicrons and
VLDL
Protein breakdown
Amino acid uptake
Protein synthesis
14.1 Control of blood glucose levels 351
Unlike the uptake of glucose into skeletal muscle and
adipose tissue, transport into liver cells is not dependent
on insulin; this hormone does, though, enhance the
conversion of glucose into glycogen, a large branched
polymer of glucose residues which serves as a readily
mobilizable storage form of glucose. Both muscle and liver
store glucose as glycogen, and insulin promotes glycogen
synthesis (glycogenesis) in both. Insulin also reciprocally
inhibits glycogen breakdown (glycogenolysis). (Whereas
skeletal muscle stores glycogen only for its own use, the
glucose derived from hepatic glycogen can be released
into the circulation as a source of fuel for other tissues, and
crucially the brain. is hepatic store of glucose is
sucient for around one day’s energy needs.)
Insulin also prevents gluconeogenesis (the synthesis of
glucose from non-carbohydrate sources) in the liver, as
well as promoting its utilization of glucose (glycolysis).
Effects on fat and protein metabolism
In adipose tissue insulin promotes lipogenesis, the
storage of fats as triglycerides, which are esters of glycerol
and fatty acids. Insulin-sensitive lipoprotein lipase
secreted by adipocytes is activated in capillaries. is acts
on circulating lipoproteins (chylomicrons and VLDL; see
Chapter 6, Section 6.1.1) to release fatty acids from
triglycerides. e fatty acids are taken up by the
adipocytes, and re-esteried with glycerol to form
triglycerides. is process is facilitated by the availability
in the cells of glycerol, derived from glucose (see above),
and by the induction of the fatty acid transporter on the
cell surface by insulin. In addition to promoting
lipogenesis, insulin opposes the breakdown of
triglycerides by intracellular hormone-sensitive lipase.
is enzyme mediates the lipolytic eects of adrenaline,
glucocorticoids, glucagon, and growth hormone. In this
way insulin antagonizes the eects of these ligands,
thereby ensuring that triglycerides are not being
simultaneously synthesized and broken down.
Insulin also favours fatty acid synthesis in adipocytes and
other tissues. Importantly, this includes the liver where
fatty acids are synthesized to be incorporated into the
triglycerides that are exported in VLDL (see Chapter 6).
Insulin leads to an increase in activity of the enzyme
acetyl CoA carboxylase, part of the fatty acid synthase
complex. e activation of this enzyme involves its
dephosphorylation; this is achieved by a protein
phosphatase which is stimulated by insulin. Again, this is
in opposition to the eects of glucagon and adrenaline,
which inhibit the carboxylase enzyme. (Fatty liver
disease, seen in alcoholism and obesity, results from
inappropriate fatty acid synthesis and the deposition of
triglycerides in the liver, and contributes to liver failure.)
Protein synthesis in muscle is promoted by insulin
through the stimulation of amino acid uptake. Insulin
also inhibits the breakdown of amino acids in the liver.
Additional actions of insulin
Insulin causes cells to take up potassium, and this is used
alongside glucose as a short-term measure for the
treatment of hyperkalaemia. It also acts on the appetite
centre in the hypothalamus of the brain to suppress
further food intake (see Section 14.7.4). In addition to the
acute eects discussed, insulin has long-term actions
brought about by alterations to protein synthesis.
14.1.4 Glucagon
e eects of insulin are opposed by the polypeptide
hormone glucagon, which ensures that blood glucose
levels do not fall too low. e cell surface receptors for
glucagon are Gs-coupled, activation leading to an
increase in cyclic AMP levels (see Chapter 2, Section
2.2.3). Glucagon promotes an increase in blood glucose
levels through eects on the liver; stimulation of glycogen
breakdown and gluconeogenesis, and an inhibition of
glycogen synthesis all result in the net release of glucose
into the bloodstream. Many of the eects of insulin on fat
and protein metabolism are also antagonized by
glucagon. In a regulatory capacity, glucagon also
stimulates the secretion of insulin by the pancreas.
14.1.5 Incretins
Incretins are peptide hormones produced by the
gastrointestinal tract. ey include glucagon-like
peptide-1 (GLP-1) and glucose-dependent insulinotropic
peptide (GIP).1 ese hormones are released in response
to food in the gastrointestinal tract, and act as an early
signal of impending glucose load into the bloodstream.
Both incretins act on Gs-coupled receptors that are highly
expressed in the pancreas, and lead to an increase in the
glucose-dependent release of insulin from -cells
(see Box 14.1). ey cause an increase in biosynthesis of
1 GIP was originally thought to slow gut motility and inhibit gastric acid
secretion, and was named gastric inhibitory peptide. ese observations
were, however, made with non-physiological concentrations of the
hormone, which was renamed according to its physiological role, but
conveniently with the same abbreviation.