Gland with both exocrine and endocrine
15-25 cm long
Location: retro-peritoneum, 2nd
Extends in an oblique, transverse position
Parts of pancreas: head, neck, body and tail
Production of Pancreatic Hormones
Alpha cells produce glucagon.
Beta cells produce insulin.
Delta cells produce somatostatin.
PP cells produce pancreatic polypeptide.
Three cell types are present,
A (glucagon secretion), B
(Insulin secretion) and D
A and D cells are located
around the perimeter while B
cells are located in the
Venous return containing
insulin flows by the A cells on
its way out of the islets
Insulin is a polypeptide hormone, composed of
two chains (A and B)
Both chains are derived from proinsulin, a
The two chains are joined by disulfide bonds.
Roles of Insulin
Acts on tissues (especially liver, skeletal
muscle, adipose) to increase uptake of glucose
and amino acids.
- without insulin, most tissues do not take in
glucose and amino acids well (except brain).
Increases glycogen production (glucose
storage) in the liver and muscle.
Stimulates lipid synthesis from free fatty acids
and triglycerides in adipose tissue.
Also stimulates potassium uptake by cells (role
in potassium homeostasis).
The insulin receptor is composed of two
subunits, and has intrinsic tyrosine kinase
Activation of the receptor results in a cascade of
Activation of glycogen synthetase. Converts
glucose to glycogen.
Inhibition of phosphoenolpyruvate
carboxykinase. Inhibits gluconeogenesis.
Increased activity of glucose transporters.
Moves glucose into cells.
Activation of acetyl CoA carboxylase. Stimulates
production of free fatty acids from acetyl CoA.
Activation of lipoprotein lipase (increases
breakdown of triacylglycerol in the circulation).
Fatty acids are then taken up by adipocytes, and
triacylglycerol is made and stored in the cell.
Major stimulus: increased blood glucose levels
- after a meal, blood glucose increases
- insulin causes uptake of glucose into tissues, so
blood glucose levels decrease.
- insulin levels decline as blood glucose declines
↑ glucose uptake in most cells
↑ glucose use and storage
↑ protein synthesis
↑ fat synthesis
Amino acids stimulate insulin release (increased uptake
into cells, increased protein synthesis).
Keto acids stimulate insulin release (increased glucose
uptake to prevent lipid and protein utilization).
Insulin release is inhibited by stress-induced increase in
- epinephrine binds to alpha adrenergic receptors on beta
- maintains blood glucose levels
Glucagon stimulates insulin secretion (glucagon has
Chemically – high levels of glucose and
amino acids in the blood
Hormonally – beta cells are sensitive to
several hormones that may inhibit or cause
Neurally – stimulation of the
parasympathetic nervous system causes
insulin to be secreted.
Structure and Actions of
Peptide hormone, 29 amino acids
Acts on the liver to cause breakdown of
glycogen (glycogenolysis), releasing glucose
into the bloodstream.
Increases production of glucose from amino
Also increases lipolysis, to free fatty acids for
Result: maintenance of blood glucose levels
Main target tissues: liver, muscle, and adipose
Binds to a Gs-coupled receptor, resulting in
increased cyclic AMP and increased PKA activity.
Also activates IP3 pathway (increasing Ca++
Glucagon prevents hypoglycemia by ↑ cell production of
Liver is primary target to maintain blood glucose levels
Activates a phosphorylase, which cleaves off a
glucose 1-phosphate molecule off of glycogen.
Inactivates glycogen synthase by phosphorylation
(less glycogen synthesis).
Increases phosphoenolpyruvate carboxykinase,
Activates lipases, breaking down triglycerides.
Inhibits acetyl CoA carboxylase, decreasing free
fatty acid formation from acetyl CoA.
Result: more production of glucose and substrates
Glucocorticoids (cortisol): stimulate
gluconeogenesis and lipolysis, and increase
breakdown of proteins.
glycogenolysis and lipolysis.
Growth hormone: stimulates glycogenolysis and
Note that these factors would complement the
effects of glucagon, increasing blood glucose
Hormonal Regulation of Nutrients
Right after a meal (resting):
- blood glucose elevated
- low glucagon, cortisol, GH, epinephrine
- insulin increases (due to increased glucose)
- Cells uptake glucose, amino acids.
- Glucose converted to glycogen, amino acids
into protein, lipids stored as triacylglycerol.
- Blood glucose maintained at moderate levels.
A few hours after a meal (active):
- blood glucose levels decrease
- insulin secretion decreases
- increased secretion of glucagon, cortisol, GH,
- glucose is released from glycogen stores
- increased lipolysis (beta oxidation)
- glucose production from amino acids
increases (oxidative deamination;
- decreased uptake of glucose by tissues
- blood glucose levels maintained
Hormonal Regulation of Nutrients
Rate at which a molecule is broken down and resynthesized.
Average daily turnover for carbohydrates is 250 g/day.
Some glucose is reused to form glycogen.
▪ Only need about 150 g/day.
Average daily turnover for protein is 150 g/day.
Some protein may be reused for protein synthesis.
▪ Only need 35 g/day.
▪ 9 essential amino acids.
Average daily turnover for fats is 100 g/day.
Little is actually required in the diet.
▪ Fat can be produced from excess carbohydrates.
▪ Essential fatty acids:
Linoleic and linolenic acids.
Mainly regulated by blood [glucose].
Lesser effect: blood [amino acid].
Regulated by negative feedback.
Glucose enters the brain by facilitated
Normal fasting [glucose] is 70-110 mg/dl.
When blood [glucose] increases:
Glucose binds to GLUT2 receptor protein in
β cells, stimulating the production and release
Stimulates skeletal muscle cells and adipocytes
to incorporate GLUT4 (glucose facilitated
diffusion carrier) into plasma membranes.
▪ Promotes anabolism.
Glucose homeostasis – Putting it all together
of pancreas stimulated
to release insulin into
take up more
Blood glucose level
declines to a set point;
stimulus for insulin
and stores it as
Rising blood glucose
level (e.g., after eating
meal) Homeostasis: Normal blood glucose level
(about 70-110 mg/100 mL) STIMULUS:
skipping a meal)
to release glucagon
into the blood
to the blood
Blood glucose level
rises to set point;
stimulus for glucagon
Absorption of energy.
4 hour period after eating.
Increase in insulin secretion.
At least 4 hours after the meal.
Increase in glucagon secretion.
Insulin is the major hormone that promotes
anabolism in the body.
When blood [insulin] increases:
Promotes cellular uptake of glucose.
Stimulates glycogen storage in the liver and muscles.
Stimulates triglyceride storage in adipose cells.
Promotes cellular uptake of amino acids and synthesis of
Maintains blood glucose concentration.
When blood [glucagon] increased:
Stimulates glycogenolysis in the liver (glucose-
Skeletal muscle, heart, liver, and kidneys use
fatty acids as major source of fuel (hormone-
Stimulates lipolysis and ketogenesis.
β cells of the islets of Langerhans are destroyed
by autoimmune attack which may be provoked
by environmental agent.
Killer T cells target glutamate decarboxylase in the β
Glucose cannot enter the adipose cells.
Rate of fat synthesis lags behind the rate of lipolysis.
▪ Fatty acids converted to ketone bodies, producing
Increased blood [glucagon].
Stimulates glycogenolysis in liver.
Slow to develop.
Genetic factors are
Occurs most often in
people who are
Decreased sensitivity to
insulin or an insulin
Do not usually develop
May have high blood
[insulin] or normal
Insert fig. 19.12
Change in lifestyle:
▪ Increases the amount of membrane GLUT-4 carriers in the skeletal
Increased fiber in diet.
Reduce saturated fat.
Over secretion of
Caused by an
response to a rise
in blood glucose.
Occurs in people
type II diabetes.
Insert fig. 19.13
Anabolic effects of insulin are antagonized by
the hormones of the adrenals, thyroid, and
Insulin, T3, and GH can act synergistically to
stimulate protein synthesis.
the ability of β
cells to secrete
Ability of insulin to
rise in blood
drinking solution is
reversed to normal
in 2 hrs.
Insert fig. 19.8