The Endocrine Pancreas
Regulation of Carbohydrate
Metabolism
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Pancreatic Anatomy
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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
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Pancreas
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Head of Pancreas
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Includes uncinate process
Flattened structure, 2 – 3 cm thick
Attached to the 2nd and 3rd portions of
duodenum on the right
Emerges into neck on the left
Border b/w head and neck is determined by
GDA insertion
SPDA and IPDA anastamose between the
duodenum and the right lateral border
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Neck of Pancreas
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2.5 cm in length
Straddles SMV and PV
Antero-superior surface supports the pylorus
Superior mesenteric vessels emerge from the
inferior border
Posteriorly, SMV and splenic vein confluence
to form portal vein
Posteriorly, mostly no branches to pancreas
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Body of Pancreas
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Elongated, long structure
Anterior surface, separated from
stomach by lesser sac
Posterior surface, related to aorta, lt.
adrenal gland, lt. renal vessels and
upper 1/3rd of lt. kidney
Splenic vein runs embedded in the post.
Surface
Inferior surface is covered by transverse
mesocolon
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Tail of Pancreas
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Narrow, short segment
Lies at the level of the 12th thoracic
vertebra
Ends within the splenic hilum
Lies in the splenophrenic ligament
Anteriorly, related to splenic flexure of
colon
May be injured during splenectomy
(fistula)
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Pancreatic Duct
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Main duct (Wirsung) runs the entire length of
pancreas
Joins CBD at the ampulla of Vater
2 – 4 mm in diameter, 20 secondary branches
Ductal pressure is 15 – 30 mm Hg (vs. 7 – 17
in CBD) thus preventing damage to panc.
duct
Lesser duct (Santorini) drains superior portion
of head and empties separately into 2nd
portion of duodenum
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Arterial Supply of Pancreas
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Variety of major arterial sources (celiac, SMA
and splenic)
Celiac  Common Hepatic Artery 
Gastroduodenal Artery  Superior
pancreaticoduodenal artery which divides into
anterior and posterior branches
SMA  Inferior pancreaticoduodenal artery
which divides into anterior and posterior
branches
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Arterial Supply of Pancreas
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Anterior collateral arcade between
anterosuperior and anteroinferior PDA
Posterior collateral arcade between
posterosuperior and posteroinferior PDA
Body and tail supplied by splenic artery by
about 10 branches
Three biggest branches are
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Dorsal pancreatic artery
Pancreatica Magna (midportion of body)
Caudal pancreatic artery (tail)
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Pancreatic Arterial Supply
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Venous Drainage of Pancreas
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Follows arterial supply
Anterior and posterior arcades drain head
and the body
Splenic vein drains the body and tail
Major drainage areas are
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Suprapancreatic PV
Retropancreatic PV
Splenic vein
Infrapancreatic SMV
Ultimately, into portal vein
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Venous Drainage of the Pancreas
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Lymphatic Drainage
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Rich periacinar network that drain into
5 nodal groups
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Superior nodes
Anterior nodes
Inferior nodes
Posterior PD nodes
Splenic nodes
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Innervation of Pancreas
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Sympathetic fibers from the splanchnic
nerves
Parasympathetic fibers from the vagus
Both give rise to intrapancreatic periacinar
plexuses
Parasympathetic fibers stimulate both
exocrine and endocrine secretion
Sympathetic fibers have a predominantly
inhibitory effect
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Innervation of Pancreas
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Peptidergic neurons that secrete amines
and peptides (somatostatin, vasoactive
intestinal peptide, calcitonin generelated peptide, and galanin
Rich afferent sensory fiber network
Ganglionectomy or celiac ganglion
blockade interrupt these somatic fibers
(pancreatic pain)
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Pancreatic Hormones, Insulin and Glucagon,
Regulate Metabolism
Production of Pancreatic Hormones
by Three Cell Types
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Alpha cells produce glucagon.
Beta cells produce insulin.
Delta cells produce somatostatin.
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Islet of Langerhans Cross-section
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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
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Pancreatic Hormones, Insulin and Glucagon,
Regulate Metabolism
Figure 22-8: Metabolism is controlled by insulin and glucagon
Structure of Insulin
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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.
Roles of Insulin
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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).
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Increases glycogen production (glucose
storage) in the liver and muscle.
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Stimulates lipid synthesis from free fatty acids
and triglycerides in adipose tissue.
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Also stimulates potassium uptake by cells (role in
potassium homeostasis).
The Insulin Receptor
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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:
phosphorylation of
insulin responsive
substrates (IRS)
RAS
RAF-1
MAP-K
MAP-KK
Final
actions
Specific Targets of Insulin
Action: Carbohydrates
Increased activity of glucose transporters.
Moves glucose into cells.
Activation of glycogen synthetase. Converts
glucose to glycogen.
Inhibition of phosphoenolpyruvate
carboxykinase. Inhibits gluconeogenesis.
Specific Targets of Insulin
Action: Lipids
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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
Regulation of Insulin Release
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Major stimulus: increased blood glucose
levels
- after a meal, blood glucose increases
- in response to increased glucose, insulin is
released
- insulin causes uptake of glucose into
tissues, so blood glucose levels decrease.
- insulin levels decline as blood glucose
declines
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Insulin Action on Cells:
Dominates in Fed State Metabolism
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 glucose uptake in most cells
(not active muscle)
 glucose use and storage
 protein synthesis
 fat synthesis
Insulin Action on Cells:
Dominates in Fed State Metabolism
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Insulin: Summary and Control Reflex
Loop
Other Factors Regulating Insulin
Release
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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).
Structure and Actions of
Glucagon
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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.
Mechanism of Action of
Glucagon
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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++)
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Glucagon Action on Cells:
Dominates in Fasting State Metabolism
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Glucagon prevents hypoglycemia by  cell
production of glucose
Liver is primary target to maintain blood glucose
levels
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Glucagon Action on Cells: Dominates in Fasting
State Metabolism
Targets of Glucagon Action
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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
Regulation of Glucagon Release
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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.
Other Factors Regulating
Glucose Homeostasis
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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.
Hormonal Regulation of Nutrients
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Right after a meal (resting):
- blood glucose elevated
- glucagon, cortisol, GH, epinephrine low
- 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.
Hormonal Regulation of Nutrients
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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
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Turnover Rate
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Rate at which a molecule is broken down and
resynthesized.
Average daily turnover for carbohydrates is 250 g/day.
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Some glucose is reused to form glycogen.
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Only need about 150 g/day.
Average daily turnover for protein is 150 g/day.
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Some protein may be reused for protein synthesis.
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Only need 35 g/day.
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9 essential amino acids.
Average daily turnover for fats is 100 g/day.
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Little is actually required in the diet.
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Fat can be produced from excess carbohydrates.
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Essential fatty acids:
 Linoleic and linolenic acids.
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Regulation of Energy Metabolism
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Energy reserves:
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Molecules that
can be oxidized for
energy are derived
from storage
molecules (glycogen,
protein, and fat).
Circulating
substrates:
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Molecules absorbed
through small
intestine and carried
to the cell for use in
cell respiration.
Insert fig. 19.2
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Pancreatic Islets (Islets of
Langerhans)
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Alpha cells secrete glucagon.
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Stimulus is decrease in
blood [glucose].
Stimulates glycogenolysis
and lipolysis.
Stimulates conversion of
fatty acids to ketones.
Beta cells secrete insulin.
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Stimulus is increase in blood
[glucose].
Promotes entry of glucose
into cells.
Converts glucose to
glycogen and fat.
Aids entry of amino acids
into cells.
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Energy Regulation of Pancreas
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Islets of Langerhans contain 3 distinct
cell types:
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a cells:
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b cells:
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Secrete glucagon.
Secrete insulin.
D cells:
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Secrete somatostatin.
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Regulation of Insulin and
Glucagon
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Mainly regulated by blood [glucose].
Lesser effect: blood [amino acid].
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Regulated by negative feedback.
Glucose enters the brain by facilitated
diffusion.
Normal fasting [glucose] is 65–105
mg/dl.
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Regulation of Insulin and
Glucagon
(continued)
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When blood [glucose] increases:
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Glucose binds to GLUT2 receptor protein in
b cells, stimulating the production and
release of insulin.
Insulin:
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Stimulates skeletal muscle cells and
adipocytes to incorporate GLUT4 (glucose
facilitated diffusion carrier) into plasma
membranes.
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Promotes anabolism.
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Oral Glucose Tolerance Test
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Measurement of
the ability of b
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
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Regulation of Insulin and
Glucagon
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Parasympathetic nervous system:
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Sympathetic nervous system:
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Stimulates insulin secretion.
GLP-1:
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Stimulates glucagon secretion.
GIP:
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Stimulates insulin secretion.
Stimulates insulin secretion.
CCK:
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Stimulates insulin secretion.
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Regulation of Insulin and
Glucagon Secretion
(continued)
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Glucose homeostasis – Putting it all
together
Insulin
Beta cells
of pancreas stimulated
to release insulin into
the blood
High blood
glucose level
STIMULUS:
Rising blood glucose
level (e.g., after eating
a carbohydrate-rich
meal)
Body
cells
take up more
glucose
Liver takes
up glucose
and stores it as
glycogen
Homeostasis: Normal blood glucose level
(about 90 mg/100 mL)
Blood glucose level
rises to set point;
stimulus for glucagon
release diminishes
Figure 26.8
Blood glucose level
declines to a set point;
stimulus for insulin
release diminishes
Liver
breaks down
glycogen and
releases glucose
to the blood
STIMULUS:
Declining blood
glucose level
(e.g., after
skipping a meal)
Alpha
cells of
pancreas stimulated
to release glucagon
into the blood
Glucagon
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Hormonal Regulation of
Metabolism
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Absorptive state:
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Absorption of energy.
4 hour period after eating.
Increase in insulin secretion.
Postabsorptive state:
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Fasting state.
At least 4 hours after the meal.
Increase in glucagon secretion.
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Absorptive State
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Insulin is the major hormone that promotes
anabolism in the body.
When blood [insulin] increases:
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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.
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Postabsorptive State
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Maintains blood glucose concentration.
When blood [glucagon] increased:
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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.
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Effect of Feeding and Fasting on
Metabolism
Insert fig. 19.10
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Diabetes Mellitus
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Chronic high blood [glucose].
2 forms of diabetes mellitus:
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Type I: insulin dependent diabetes (IDDM).
Type II: non-insulin dependent diabetes
(NIDDM).
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Comparison of Type I and Type
II Diabetes Mellitus
Insert table 19.6
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Type I Diabetes Mellitus
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b cells of the islets of Langerhans are
destroyed by autoimmune attack which may
be provoked by environmental agent.
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Killer T cells target glutamate decarboxylase in the
b cells.
Glucose cannot enter the adipose cells.
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Rate of fat synthesis lags behind the rate of
lipolysis.
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Fatty acids converted to ketone bodies, producing
ketoacidosis.
Increased blood [glucagon].
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Stimulates glycogenolysis in liver.
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Consequences of Uncorrected Deficiency
in Type I Diabetes Mellitus
Insert fig. 19.11
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Type II Diabetes Mellitus
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Slow to develop.
Genetic factors are
significant.
Occurs most often in
people who are
overweight.
Decreased sensitivity to
insulin or an insulin
resistance.
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Obesity.
Do not usually develop
ketoacidosis.
May have high blood
[insulin] or normal
[insulin].
Insert fig. 19.12
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Treatment in Diabetes
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Change in lifestyle:
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Increase exercise:
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Increases the amount of membrane GLUT-4 carriers in
the skeletal muscle cells.
Weight reduction.
Increased fiber in diet.
Reduce saturated fat.
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Hypoglycemia
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Over secretion of
insulin.
Reactive
hypoglycemia:
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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
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Metabolic Regulation
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Anabolic effects of insulin are
antagonized by the hormones of the
adrenals, thyroid, and anterior pituitary.
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Insulin, T3, and GH can act synergistically
to stimulate protein synthesis.