The pancreas regulates carbohydrate metabolism through the hormones insulin and glucagon. Insulin promotes anabolism by stimulating glucose uptake and glycogen/lipid synthesis. Glucagon promotes catabolism by stimulating glycogenolysis and gluconeogenesis to maintain blood glucose levels. Disorders like diabetes occur when insulin/glucagon secretion is impaired, leading to chronic high or low blood glucose.

1. Regulation of Carbohydrate Metabolism

2.  Gland with both exocrine and endocrine
functions
 15-25 cm long
 60-100 g
 Location: retro-peritoneum, 2nd
lumbar vertebral
level
 Extends in an oblique, transverse position
 Parts of pancreas: head, neck, body and tail

4. Production of Pancreatic Hormones
Alpha cells produce glucagon.
Beta cells produce insulin.
Delta cells produce somatostatin.
PP cells produce pancreatic polypeptide.

5.  Three cell types are present,
A (glucagon secretion), B
(Insulin secretion) and D
(Somatostatin secretion)
 A and D cells are located
around the perimeter while B
cells are located in the
interior
 Venous return containing
insulin flows by the A cells on
its way out of the islets

6.  Insulin is a polypeptide hormone, composed of
two chains (A and B)
 Both chains are derived from proinsulin, a
prohormone.
 The two chains are joined by disulfide bonds.

7. 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).

8.  The insulin receptor is composed of two
subunits, and has intrinsic tyrosine kinase
activity.
 Activation of the receptor results in a cascade of
phosphorylation events.

10. Activation of glycogen synthetase. Converts
glucose to glycogen.
Inhibition of phosphoenolpyruvate
carboxykinase. Inhibits gluconeogenesis.
Increased activity of glucose transporters.
Moves glucose into cells.

11. 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.
lipoprotein
lipase

12.  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

13.  ↑ glucose uptake in most cells
 ↑ glucose use and storage
 ↑ protein synthesis
 ↑ fat synthesis

15.  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
adrenal epinephrine
- epinephrine binds to alpha adrenergic receptors on beta
cells
- maintains blood glucose levels
 Glucagon stimulates insulin secretion (glucagon has
opposite actions).

16.  Chemically – high levels of glucose and
amino acids in the blood
 Hormonally – beta cells are sensitive to
several hormones that may inhibit or cause
insulin secretion
 Neurally – stimulation of the
parasympathetic nervous system causes
insulin to be secreted.
16

17. 17
• Decreased blood glucose
concentration.
• Increased blood insulin concentration.
• Sympathetic stimulation.

18. Structure and Actions of
Glucagon
Peptide hormone, 29 amino acids
Acts on the liver to cause breakdown of
glycogen (glycogenolysis), releasing glucose
into the bloodstream.
Inhibits glycolysis
Increases production of glucose from amino
acids (gluconeogenesis).
Also increases lipolysis, to free fatty acids for
metabolism.
Result: maintenance of blood glucose levels
during fasting.

19.  Main target tissues: liver, muscle, and adipose
tissue
 Binds to a Gs-coupled receptor, resulting in
increased cyclic AMP and increased PKA activity.
 Also activates IP3 pathway (increasing Ca++
)

20.  Glucagon prevents hypoglycemia by ↑ cell production of
glucose.
 Liver is primary target to maintain blood glucose levels

22.  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,
stimulating gluconeogenesis.
 Activates lipases, breaking down triglycerides.
 Inhibits acetyl CoA carboxylase, decreasing free
fatty acid formation from acetyl CoA.
 Result: more production of glucose and substrates
for metabolism

23.  Increased blood glucose levels inhibit glucagon
release.
 Amino acids stimulate glucagon release (high
protein, low carbohydrate meal).
 Stress: epinephrine acts on beta-adrenergic
receptors on alpha cells, increasing glucagon
release (increases availability of glucose for
energy).
 Insulin inhibits glucagon secretion.

24.  Glucocorticoids (cortisol): stimulate
gluconeogenesis and lipolysis, and increase
breakdown of proteins.
 Epinephrine/norepinephrine: stimulates
glycogenolysis and lipolysis.
 Growth hormone: stimulates glycogenolysis and
lipolysis.
 Note that these factors would complement the
effects of glucagon, increasing blood glucose
levels.

25. 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.

26. A few hours after a meal (active):
- blood glucose levels decrease
- insulin secretion decreases
- increased secretion of glucagon, cortisol, GH,
epinephrine
- glucose is released from glycogen stores
(glycogenolysis)
- increased lipolysis (beta oxidation)
- glucose production from amino acids
increases (oxidative deamination;
gluconeogenesis)
- decreased uptake of glucose by tissues
- blood glucose levels maintained
Hormonal Regulation of Nutrients

27.  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.

28.  Mainly regulated by blood [glucose].
 Lesser effect: blood [amino acid].
 Regulated by negative feedback.
 Glucose enters the brain by facilitated
diffusion.
 Normal fasting [glucose] is 70-110 mg/dl.

29.  When blood [glucose] increases:
 Glucose binds to GLUT2 receptor protein in
β cells, stimulating the production and release
of insulin.
 Insulin:
 Stimulates skeletal muscle cells and adipocytes
to incorporate GLUT4 (glucose facilitated
diffusion carrier) into plasma membranes.
▪ Promotes anabolism.

32.  Glucose homeostasis – Putting it all together
Figure 26.8
Insulin
Beta cells
of pancreas stimulated
to release insulin into
the blood
Body
cells
take up more
glucose
Blood glucose level
declines to a set point;
stimulus for insulin
release diminishes
Liver takes
up glucose
and stores it as
glycogen
High blood
glucose level
STIMULUS:
Rising blood glucose
level (e.g., after eating
a carbohydrate-rich
meal) Homeostasis: Normal blood glucose level
(about 70-110 mg/100 mL) STIMULUS:
Declining blood
glucose level
(e.g., after
skipping a meal)
Alpha
cells of
pancreas stimulated
to release glucagon
into the blood
Glucagon
Liver
breaks down
glycogen and
releases glucose
to the blood
Blood glucose level
rises to set point;
stimulus for glucagon
release diminishes

33.  Absorptive state:
 Absorption of energy.
 4 hour period after eating.
 Increase in insulin secretion.
 Postabsorptive state:
 Fasting state.
 At least 4 hours after the meal.
 Increase in glucagon secretion.

34.  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
proteins.

35.  Maintains blood glucose concentration.
 When blood [glucagon] increased:
 Stimulates glycogenolysis in the liver (glucose-
6-phosphatase).
 Stimulates gluconeogenesis.
 Skeletal muscle, heart, liver, and kidneys use
fatty acids as major source of fuel (hormone-
sensitive lipase).
 Stimulates lipolysis and ketogenesis.

36. Insert fig. 19.10

37. Figure 22-8: Metabolism is controlled by insulin and glucagon

38.  Chronic high blood [glucose].
 2 forms of diabetes mellitus:
 Type I: insulin dependent diabetes (IDDM).
 Type II: non-insulin dependent diabetes (NIDDM).

39. Insert table 19.6

40.  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
cells.
 Glucose cannot enter the adipose cells.
 Rate of fat synthesis lags behind the rate of lipolysis.
▪ Fatty acids converted to ketone bodies, producing
ketoacidosis.
 Increased blood [glucagon].
 Stimulates glycogenolysis in liver.

41. Insert fig. 19.11

42.  Slow to develop.
 Genetic factors are
significant.
 Occurs most often in
people who are
overweight.
 Decreased sensitivity to
insulin or an insulin
resistance.
 Obesity.
 Do not usually develop
ketoacidosis.
 May have high blood
[insulin] or normal
[insulin].
Insert fig. 19.12

43.  Change in lifestyle:
 Increase exercise:
▪ Increases the amount of membrane GLUT-4 carriers in the skeletal
muscle cells.
 Weight reduction.
 Increased fiber in diet.
 Reduce saturated fat.

44.  Over secretion of
insulin.
 Reactive
hypoglycemia:
 Caused by an
exaggerated
response to a rise
in blood glucose.
 Occurs in people
who are
genetically
predisposed to
type II diabetes.
Insert fig. 19.13

45.  Anabolic effects of insulin are antagonized by
the hormones of the adrenals, thyroid, and
anterior pituitary.
 Insulin, T3, and GH can act synergistically to
stimulate protein synthesis.

46.  Measurement of
the ability of β
cells to secrete
insulin.
 Ability of insulin to
lower blood
glucose.
 Normal person’s
rise in blood
[glucose] after
drinking solution is
reversed to normal
in 2 hrs.
Insert fig. 19.8