The pancreas has both exocrine and endocrine functions. The exocrine pancreas secretes enzymes to aid digestion. The endocrine pancreas contains islets of Langerhans that secrete hormones like insulin and glucagon to regulate blood sugar levels. Insulin is produced by beta cells in response to rising blood glucose, and promotes the uptake and storage of glucose in tissues. Disorders of the exocrine pancreas cause maldigestion, while disorders of the endocrine pancreas can lead to diabetes.

1. Pancreas
Endocrine & Exocrine Pancreas
Insulin & Glucagon
BreadWinnerzAssociation

2. The Pancreas:
• Is a soft, lobulated organ that stretches obliquely across the
posterior abdominal wall in the epigastric region.
• Situated behind stomach & extends from the duodenum to the
spleen.
• Has both exocrine & endocrine functions.
• The endocrine pancreas is composed of the islets of Langerhans.
– Contains several hormone-producing cells.
– Produces hormones which play key roles in carbohydrate metabolism.
– Dysfunction causes diabetes mellitus.
• The exocrine pancreas contains acini, which secretes pancreatic
juice into the duodenum through the pancreatic ducts.
– Disorders causes maldigestion of fat & steatorrhea (fatty stools).
– Dysfunction results from inflammation (acute/chronic pancreatitis),
neoplasm (pancreatic carcinoma), or duct obstruction by stones or
abnormally viscid mucus (cystic fibrosis).
• Both exocrine & endocrine pancreatic dysfunction occur together in
some patients. BreadWinnerzAssociation

3. Surface Marking:
• Lies across the transpyloric plane.
• The head lies below & to the right.
• The neck lies on the plane.
• The body & tail lie above & to the left.
• The transpyloric plane passes through the tips of the
9th costal cartilages on the 2 sides-i.e., the point where
the lateral margin of the rectus abdominis (linea
semilunaris) crosses the costal margin.
– It lies at the level of L1 vertebrae body.
– The plane passes through the pylorus of stomach, the
duodenojejunal junction, the neck of pancreas, & the hila
of kidneys.
BreadWinnerzAssociation

4. Illustration 1.1: Arrangement of
peritoneum
BreadWinnerzAssociation

5. Vasculature:
• Blood supply:
– Arteries: Supplied by splenic & the superior and inferior
pancreaticoduodenal arteries.
– Veins: Corresponding veins drain into the portal system.
• Lymph drainage:
– Lymph nodes are situated along the arteries that supply
the gland.
– Ultimately drain into the celiac & the superior mesenteric
lymph nodes.
• Nerve supply:
– Sympathetic & parasympathetic (vagal) nerve fibers.
BreadWinnerzAssociation

6. Anatomy-Exocrine Pancreas:
• Is a solid organ.
• Lies transversely across posterior abdominal wall deep within
epigastrium. (retroperitoneal organ)
• Firmly fixed in front of the abdominal aorta & 1st and 2nd lumbar
vertebrae.
• Normally, is abt 15cm long, although it weighs <110g.
• Divided into 4 parts: head, including uncinate process; neck; body;
& tail.
• The head lies in the curved space btw 1st, 2nd & 3rd portions of
duodenum.
• The uncinate process is the portion of the head that extends to the
left behind the superior mesenteric vessels.
• The neck is the constricted part and connects the head & the body.
• The body is situated horizontally in the retroperitoneal space.
• The tail extend towards the hilum of the spleen.
BreadWinnerzAssociation

7. Illustration 1.2
Reproduced, with permission, from Way LW [editor]: Current Surgical Diagnosis & Treatment, 10th ed. Originally
published by Appleton & Lange. Copyright © 1998 by The McGraw-Hill Companies, Inc.
BreadWinnerzAssociation

8. (cont’d)
• The exocrine pancreas is drained by a major central duct
called duct of Wirsung.
• This duct runs the length of the gland.
• Duct normally is about 3-4mm in diameter.
• Pancreatic duct enters the duodenum at the major
duodenal papilla alongside the common bile duct.
• The sphincter of Oddi surrounds both ducts.
• In abt one third of individuals, the duct of Wirsung & the
common bile duct join to form a common channel before
terminating at the ampulla of Vater at about the middle
portion of second part of duodenum.
• The accessory pancreatic duct, (duct of Santorini), runs
from the head & body of the gland to enter the duodenum
abt 2cm proximal to the duodenal papilla.
BreadWinnerzAssociation

9. Anatomy-Endocrine Pancreas:
• Endocrine pancreas is composed of nests of cells called the
islets of Langerhans.
• There are more than 1 million islets in the human pancreas,
many of which contain several hundred cells.
• The endocrine pancreas has great reserve capacity; >70%
of the B cells must be lost before dysfunction occurs.
• The islets are much more vascularized than the exocrine
pancreatic tissues.
• Blood flow is thought to proceed from the center of the
islet to the periphery, thereby allowing insulin produced by
the central B cells to inhibit glucagon release by
A cells.
BreadWinnerzAssociation

10. (cont’d)
Cell Type Proportion Hormone(s)
A cells <20% of the islet cells Glucagon, proglucagon,
glucagon-like peptides
(GLP)
B cells 80% of the islet cells Insulin, proinsulin, C-
peptide, amylin, GABA
D cells Few in number Somatostatin
PP cells (a.k.a. F cells) In islets in posterior lobe of
head of pancreas
Pancreatic polypeptide
• There are 4 cell types within the islets, each of which produces a different
major secretory product.
• Blood from the islets then drains into the hepatic portal vein.
• Thus, secretory products pass directly into the liver before proceeding into
systemic circulation.
BreadWinnerzAssociation

11. Illustration 1.3
Schematic representation of a normal rat (right) & human (left) islet showing the
topographic relationships of the major cell types.
BreadWinnerzAssociation

12. Physiology:
Pancreatic Juice & Enzymes
BreadWinnerzAssociation

13. Pancreatic juice: (exocrine)
• Abt 1.5L of pancreatic juice is secreted each day.
• Pancreatic juice contains water, ions, & a variety of
proteins.
• The principal ions are HCO₃⁻, Cl⁻, Na⁺, & K⁺.
– Of these, HCO₃⁻ is particularly important.
• The alkaline nature of pancreatic juice plays a major role in
neutralizing the gastric acid entering the duodenum with
ingested food (chyme) from the stomach.
• Pancreatic enzymes aid in the intraluminal phase of
digestion & absorption of fats, carbs, & proteins.
• The rest are plasma proteins, mucoproteins, & trypsin
inhibitors.
BreadWinnerzAssociation

14. Pancreatic enzymes:
Secreted in active form(s): Secreted as inactive proenzymes: (zymogens)
Lipase Trypsinogen
Amylase Chymotrypsinogen
Deoxyribonuclease Proelastase
Ribonuclease Procarboxypeptidase
Phospholipase A2
BreadWinnerzAssociation
• Activation of zymogens within the acinar cell might otherwise
lead to acute pancreatitis & pancreatic autodigestion.

15. Secretion of Pancreatic Juice:
• Secretion is controlled primarily by:
– Secretin &
– Cholecystokinin (CCK); both produced by specialized enteroendocrine cells of
the duodenal mucosa.
• Also controlled in part by a reflex mechanism:
– Ach released by the vagus nerve acts like CCK on acinar cells to cause
discharge of zymogen granules.
BreadWinnerzAssociation
Hormone Trigger for release Target cell(s) Action(s)
Secretin • Gastric acid
• Products of protein
digestion in
duodenum
Pancreatic duct
cells
Cause an
outpouring of very
alkaline pancreatic
juice
CCK • Products of protein
& fat digestion in
the duodenum
Acinar cells Release of
enzymes from
zymogen granules.

16. Physiology:
Insulin
BreadWinnerzAssociation

17. Insulin Synthesis:
• Insulin plays a major role in fuel homeostasis-it plays an
important role in storing the excess energy.
• Insulin is a protein composed of 2 peptide chains (α & β
chains), connected by 2 disulfide bonds.
• Preproinsulin is synthesized in the ribosomes & enters the
endoplasmic reticulum of B cells.
– From here, it is cleaved by microsomal enzymes to form
proinsulin.
• Transported to the Golgi apparatus, packaged into
secretory vesicles.
• In the secretory vesicles, proinsulin is cleaved at two sites
to form insulin & the biologically inactive C peptide
fragment.
• Liver catabolizes ~50% of insulin
BreadWinnerzAssociation

18. Insulin Secretion:
• Glucose is the primary physiologic stimulant of insulin
release.
• Other factors such as amino acids ingested with a meal or
vagal stimulation can cause insulin release.
– Amino acids strongly potentiate the glucose stimulus for insulin
secretion.
• Glucose enters B cells via glucose transporter proteins
(GLUT 2).
• ATP formed via glucose metabolism inhibits K⁺ efflux from
the B cell. (ATP-sensitive potassium channels)
• Depolarization occurs; allowing Ca⁺⁺ to enter-through
voltage-gated calcium channels.
• This triggers exocytosis of insulin-containing granules.
BreadWinnerzAssociation

19. BreadWinnerzAssociation
Illustration 1.4
Glucose-stimulated
insulin release

20. Factors & Conditions That Increase/Decrease
Insulin Secretion
Increase Insulin Secretion: Decrease Insulin Secretion:
Increased blood glucose Decreased blood glucose
Increased blood free fatty acids Fasting
Increased blood amino acids Somatostatin
Gastrointestinal hormones (gastrin, CCK,
secretin, GIP)
Α-Adrenergic activity
Leptin
Glucagon, growth hormone, cortisol
Parasympathetic stimulation; Ach
Β-Adrenergic stimulation
Insulin resistance; obesity
Sulfonylurea drugs (glyburide,
tolbutamide)
BreadWinnerzAssociation

21. Mechanism of Action:
• Insulin exerts its effects by binding to insulin receptors
present on the surfaces of target cells (liver, muscle, &
fat).
• Binding of insulin to its receptor (e.g. of an enzyme-
linked receptor) causes:
– activation of a tyrosine kinase region
– autophosphorylation of the receptor. (ß-subunit)
• This amplifies downstream signaling molecules,
ultimately leading to the biologic effects of insulin;
– Translocation of GLUT 4 glucose transporter to the plasma
membranes of muscle & fat cells.
BreadWinnerzAssociation

22. Insulin Effects:
• Insulin promotes fuel storage (anabolism) & prevents catabolism.
– Increase glucose uptake in abt 80% of the body’s cells; esp. muscle &
fat cells but not neurons in brain.
• In liver; insulin stimulates glycogen synthesis & storage.
– Insulin inhibits hepatic glucose output by inhibiting gluconeogenesis &
glycogenolysis.
– Also promotes formation of fatty acid precursors.
• Insulin stimulates lipogenesis, leading to the increased synthesis of
VLDLs; increasing fat stored.
• Insulin stimulates glucose uptake both in muscle & fat by causing
the rapid translocation of GLUT-4 to the surface of these cells.
• In muscle, insulin causes glycogen & protein synthesis and inhibits
glycogen catabolism.
BreadWinnerzAssociation

23. Illustration 1.5
BreadWinnerzAssociation
The receptor tyrosine kinase activity
begins a cascade of cell
phosphorylation that
increases/decreases the activity of
the enzymes, including insulin
receptor substrates (IRS), that
mediate the effects on glucose, fat, &
protein metabolism.

24. BreadWinnerzAssociation
Physiology:
Glucagon

25. Glucagon Synthesis:
• Is produced by the proteolytic processing of
proglucagon.
• Apart from pancreas, proglucagon is also
expressed in the intestine & brain.
• Pancreatic glucagon opposes the effects of
insulin.
• Circulatory half-life is 3-6 min.
• Glucagon is metabolized in liver (25%) &
kidneys.
BreadWinnerzAssociation

26. Regulation of Secretion:
• Glucagon secretion is inhibited by glucose.
• Fatty acids & ketones inhibit glucagon
secretion.
• GABA (from B cells) is also thought to inhibit
glucagon release.
• Catecholamines & cortisol stimulate glucagon
release.
BreadWinnerzAssociation

27. Mechanism of Action:
• Glucagon binds to a glucagon receptor present on
hepatocytes.
• This promotes interaction with a stimulatory G protein,
which in turn activates adenylyl cyclase.
• CAMp, generated by adenylyl cyclase, activates protein
kinase regulator protein,
• Which activates protein kinase,
• Which activates phosphorylase b kinase,
• Which converts phosphorylase-b into phosphorylase-a,
• Which promotes degradation of glycogen into glucose-1-
phosphate.
• Which is then dephosphorylated; & the glucose released
from hepatocytes.
BreadWinnerzAssociation

28. Effects:
• Glucagon affects metabolism by its actions in the
liver & elsewhere.
• It counters the effects of insulin by acting in a
catabolic fashion to maintain serum glucose
levels.
• It stimulates hepatic glucose output.
• It stimulates glycogenolysis & gluconeogenesis.
• Also stimulates fatty acid oxidation &
ketogenesis; providing an alternative fuel that
can be used by the brain when glucose is not
available.
BreadWinnerzAssociation

29. The End!
Halleluyah!
BreadWinnerzAssociation