The document discusses a lecture on the endocrine pancreas and its regulation of carbohydrate metabolism. Specifically, it summarizes the anatomy of the pancreas, describes the three types of cells in the pancreatic islets of Langerhans that secrete insulin, glucagon, and somatostatin, and explains how insulin and glucagon work in opposition to maintain blood glucose levels by regulating glucose uptake and storage versus breakdown and production.
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Pancrease
1. Dr. Zeenat Hussain
Foundation
“The ultimate value of life depends upon
awareness and the power of contemplation
rather than upon mere survival.”
Aristotle
Dr. Zeenat Hussain Foundation is working to
create awareness against the diseases
among the common people of Pakistan. This
lecture is also a part of this campaign. Your
cooperation and feed back shall be highly
appreciated.
4. Pancreas- Brief History
Herophilus,
Greek
surgeon first described
pancreas.
Wirsung discovered the
pancreatic duct in 1642.
Pancreas as a secretory
gland was investigated by
Graaf in 1671.
R.
Fitz
established
pancreatitis as a disease
in 1889.
Whipple performed the
first
pancreaticoduodenectomy in 1935 Duct of
Santorini
Duct of
Wirsung
5. Pancreatic Anatomy
Gland
with both exocrine and endocrine
functions
15-25 cm long in length
60-100 grams in weight
Location: retro-peritoneum, 2nd lumbar vertebral
level
Extends in an oblique, transverse position
Parts of pancreas: head, neck, body and tail
7. 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
8. 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
9. Body of Pancreas
Elongated, long structure
Anterior surface, separated from stomach
by lesser sac
Posterior surface, related to aorta, adrenal
gland, renal vessels and upper 1/3 rd of
kidney
Splenic vein runs embedded in the post.
Surface
Inferior surface is covered by transverse
mesocolon
10. Tail of Pancreas
Narrow, short segment
Lies at the level of the 12 th
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)
11. Pancreatic Duct
Main duct (Wirsung) runs the entire length of
pancreas
2 – 4 mm in diameter, 20 secondary branches
Ductal pressure is 15 – 30 mm Hg thus
preventing damage to pancreatic duct
Lesser duct (Santorini) drains superior portion of
head and empties separately into 2nd portion of
duodenum
12. 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 (Superior mesentric artery) Inferior
pancreaticoduodenal artery which divides into
anterior and posterior branches
14. 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
18. Production of Pancreatic Hormones
by Three Cell Types
Alpha cells produce glucagon.
Beta cells produce insulin.
Delta cells produce somatostatin.
19. 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
20. 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
Increased activity of glucose transporters.
Moves glucose into cells.
Activation of glycogen synthetase. Converts
glucose to glycogen.
Inhibition of phosphoenolpyruvate
carboxykinase. Inhibits gluconeogenesis.
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.
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
27. 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
31. 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).
32. 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.
33. 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++)
34. Glucagon Action on Cells:
Dominates in Fasting State
Metabolism
Glucagon
prevents hypoglycemia by ↑ cell
production of glucose
Liver is primary target to maintain blood glucose
levels
36. 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
37. 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.
38. 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.
39. 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.
40. Hormonal Regulation of Nutrients
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
41. 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
42. 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.
43.
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
STIMULUS:
Declining blood
glucose level
(e.g., after
skipping a meal)
Alpha
cells of
pancreas stimulated
to release glucagon
into the blood
Liver
breaks down
glycogen and
releases glucose
to the blood
Glucagon