The document discusses the endocrine pancreas and regulation of carbohydrate metabolism. It describes that the pancreas has both exocrine and endocrine functions. The pancreatic islets contain three main cell types - alpha cells which produce glucagon, beta cells which produce insulin, and delta cells which produce somatostatin. Insulin and glucagon work to regulate blood glucose levels through their opposing actions on carbohydrate, lipid, and protein metabolism.

1. The Endocrine Pancreas
Regulation of Carbohydrate
Metabolism

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Pancreatic Anatomy
 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
 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
 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
 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
 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
 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
 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
 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
 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
 Follows arterial supply
 Anterior and posterior arcades drain head
and the body
 Splenic vein drains the body and tail
 Major drainage areas are
 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
 Rich periacinar network that drain into 5
nodal groups
 Superior nodes
 Anterior nodes
 Inferior nodes
 Posterior PD nodes
 Splenic nodes

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Innervation of Pancreas
 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
 Peptidergic neurons that secrete
amines and peptides (somatostatin,
vasoactive intestinal peptide, calcitonin
gene-related 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

18. Production of Pancreatic Hormones
by Three Cell Types
Alpha cells produce glucagon.
Beta cells produce insulin.
Delta cells produce somatostatin.

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Islet of Langerhans Cross-section
 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

21. Structure of Insulin
 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.

22. 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).

23. The Insulin Receptor
 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

24. Specific Targets of Insulin
Action: Carbohydrates
Activation of glycogen synthetase. Converts
glucose to glycogen.
Inhibition of phosphoenolpyruvate
carboxykinase. Inhibits gluconeogenesis.
Increased activity of glucose transporters.
Moves glucose into cells.

25. Specific Targets of Insulin
Action: Lipids
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

26. Regulation of Insulin Release
 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
 ↑ glucose uptake in most cells
(not active muscle)
 ↑ glucose use and storage
 ↑ protein synthesis
 ↑ fat synthesis

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Insulin Action on Cells:
Dominates in Fed State Metabolism

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Insulin: Summary and Control Reflex
Loop

30. Other Factors Regulating
Insulin Release
 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).

31. 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.

32. Mechanism of Action of
Glucagon
 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 prevents hypoglycemia by ↑ cell
production of glucose
 Liver is primary target to maintain blood glucose
levels
Glucagon Action on Cells:
Dominates in Fasting State Metabolism

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Glucagon Action on Cells: Dominates in
Fasting State Metabolism

35. Targets of Glucagon Action
 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

36. Regulation of Glucagon
Release
 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.

37. Other Factors Regulating
Glucose Homeostasis
 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.

38. Hormonal Regulation of Nutrients
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.

39. 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

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Turnover Rate
 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.

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Regulation of Energy
Metabolism
 Energy reserves:
 Molecules that
can be oxidized for
energy are derived
from storage
molecules (glycogen,
protein, and fat).
 Circulating
substrates:
 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)
 Alpha cells secrete
glucagon.
 Stimulus is decrease in
blood [glucose].
 Stimulates glycogenolysis
and lipolysis.
 Stimulates conversion of
fatty acids to ketones.
 Beta cells secrete insulin.
 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
 Islets of Langerhans contain 3 distinct
cell types:
 α cells:

Secrete glucagon.
 β cells:

Secrete insulin.
 ∆ cells:

Secrete somatostatin.

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Regulation of Insulin and
Glucagon
 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 65–105
mg/dl.

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Regulation of Insulin and
Glucagon (continued)
 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.

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Oral Glucose Tolerance Test
 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

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Regulation of Insulin and
Glucagon
 Parasympathetic nervous system:
 Stimulates insulin secretion.
 Sympathetic nervous system:
 Stimulates glucagon secretion.
 GIP:
 Stimulates insulin secretion.
 GLP-1:
 Stimulates insulin secretion.
 CCK:
 Stimulates insulin secretion.

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Regulation of Insulin and
Glucagon Secretion (continued)

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 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 90 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

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Hormonal Regulation of
Metabolism
 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.

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Absorptive State
 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.

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Postabsorptive State
 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.

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Insert fig. 19.10
Effect of Feeding and Fasting
on Metabolism

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Diabetes Mellitus
 Chronic high blood [glucose].
 2 forms of diabetes mellitus:
 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
 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.

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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
 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

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Treatment in Diabetes
 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.

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Hypoglycemia
 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

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Metabolic Regulation
 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.