By Juliana Xie
Pan-creas!
• Greek: “pan” =
all; “creas” =
flesh
• Pancreas is like a
fish! Head, body,
and tail.
• Important
anatomical
relationships
Why care about the pancreas?
• The diseased pancreas can cause a LOT of trouble
•
Diabetes:
• In the United States, 25.8 million adults and children (8.3% of
population) have diabetes
• Systemic disease
• Pancreatic cancer – 4th most common cause of
cancer-related death, extremely poor prognosis
• Pancreatitis is an emergency situation
What makes the pancreas such an
important organ?
•Outline pancreatic gross and cellular
anatomy
•Discuss the normal function of the
pancreas in glucose metabolism
Pancreas: two major roles
2) Endocrine
• Produce enzymes that
CHOP (digest) food
1) Exocrine
• Control the sugar levels
in the body
A closer look: Endocrine Pancreatic cells
Islets of Langerhans!!!
Islets of Langerhans has
FOUR major cell types:
1) Alpha cell
2) Beta cell
3) Gamma cell (PP cell)
4) Delta cell
A closer look: Endocrine Pancreatic cells
1)
2)
3)
4)
•
Alpha cells  glucagon
Beta cells  insulin
Gamma cells  pancreatic polypeptide
Delta cells  somatostatin
Observe how these cells lie in close proximity of
capillaries.
Alpha cells
•
Alpha cells make up 33-46% of the human islet cells
•
Make and secrete glucagon to elevate glucose levels in
blood
Clinical correlation:
Too much glucagon – glucagonoma
-rare tumor of the alpha cells that cause up to 1000fold overproduction of glucagon
-blood glucose raises via gluconeogenesis and
lipolysis
-causes diabetes mellitus
Beta cells
•
Make up 65-80% of the cells in the islets
• Pathology:
• Type 1 diabetes mellitus
• Insulin-dependent diabetes
• Autoimmune disease
• Body cannot make insulin
• Type 2 diabetes mellitus
• Non insulin-dependent diabetes
• Body can still make insulin, but tissues are insensitive to its actions
Gamma cells
Predominantly reside in the head of the pancreas
• Makes and releases pancreatic polypeptide (PP) in
response to ingestion of food
• Inhibitory functions
• Found to be elevated in anorexia nervosa
Clinical correlation:
-too much PP – Pancreatic polypeptidoma
-can cause weight loss, diabetes mellitus
•
Delta Cells
Produce somatostatin  INHIBITORY
• Produced in multiple tissues, antigrowth effects
• Suppress the release of insulin and glucagon
•
Clinical correlation:
Too much somatostatin – somatostatinoma
-extreme reduction in secretion of insulin
and cause diabetes.
Pancreas and Glucose Homeostasis
• Glucose regulation works in a system of organs
Pancreas and Glucose Homeostasis
Clinical correlation: glucose test
• Normal fasting
blood sugar: 72 to
126 mg/dL
• After a meal: less
than 180 mg/dL
90 minutes after
eating is normal
Hormonal Regulation of
Glucose Metabolism
LUKE D. PIPER
Overview: Learning Objectives
Assuming I know what I’m doing up here, students should ultimately
be able to:
• Discuss the actions of insulin and glucagon
• Discuss the mechanisms that regulate secretion of insulin and
glucagon
• Discuss potential problems arising from poor glucose regulation
• Discuss how eating and fasting affect blood sugar, and how the
body responds
Goals of Glucose Regulation
• Get glucose into cells for utilization/storage
 Glucose is primary fuel for cellular energy
 Can be stored in liver and muscles as glycogen
• Breakdown stored energy into glucose
 Glycogen breakdown can quickly supply glucose
 Lipids and proteins can be converted to glucose
• Keep blood glucose from becoming too low or too high
 Hypo- and hyperglycemia can both be dangerous
Insulin
Insulin is stored as a
hexamer (left).
Its active form is a
monomer (below).
• Polypeptide hormone
• Produced in the Pancreas
 Specifically, the β cells of the islets of Langerhans
• Principle action: facilitates glucose uptake and glycogen synthesis
• Other actions: facilitates lipid and protein synthesis
• Insulin is primarily anabolic
Insulin: Principle Actions
• Glucose uptake
 Signaling pathway increases membrane expression of GLUT4 transporter
 Allows glucose to enter cell
 Especially important in muscle and adipose
• Muscles: energy and storage
• Adipose: long-term storage
 Note: not all cells need insulin to get glucose
• Glycogen synthesis
 Signaling pathway promotes storage of glucose as glycogen
 Especially important in liver
Insulin Action: Visual Aid
Recall: insulin is
anabolic
Insulin Regulation
• Insulin secretion is stimulated by:
 High blood glucose levels
 Amino acid ingestion
 Gastrointestinal hormones (e.g., cholecystokinin)
• Insulin secretion is inhibited by:
 Scarcity of dietary fuel
 Epinephrine
Glucagon
• Also a polypeptide hormone
• Also produced in the pancreas
 Specifically, the α cells of the islets of Langerhans
• Principle action: mobilization of stored energy
• Directly opposes most of insulin’s effects
 Pancreas coordinates release of glucagon and insulin
• Glucagon is primarily catabolic
…yep, this is it.
Glucagon: Principle Actions
• Increases blood glucose
 Triggers glycogen breakdown in liver (glycogenolysis)
 Activates glucose production pathways (gluconeogenesis)
• Elicits breakdown of stored lipids (lipolysis)
 Glycerol used in gluconeogenesis
 Free fatty acids can be made into ketone bodies
• Amino acid metabolism
 Taken up by liver; used in gluconeogenesis
• Theme: glucagon engages energy reserves
Glucagon Action: Visual Aid
Glucagon operates via G-protein signaling
to activate protein kinase A. Here, PKA
activates enzymes involved in glycogen
breakdown and deactivates enzymes
involved in glycogen synthesis.
In adipose, the same type of pathway
is used. There, the pathway targets
enzymes involved in lipolysis.
Glucagon Regulation
• Glucagon secretion is stimulated by:
 Low blood glucose
 Amino acid ingestion
 Epinephrine
• Glucagon secretion is inhibited by:
 High blood glucose
 Insulin
Super Fun and Totally Cool Mnemonic
• Insulin gets glucose into cells
 (so that they can use it or store it)
• Glucagon is for when the glucose is gone
 (and you need to mobilize storage)
Overview: Learning Objectives
Assuming I know what I’m doing up here, students should ultimately
be able to:
• Discuss the actions of insulin and glucagon
• Discuss the mechanisms that regulate secretion of insulin and
glucagon
• Discuss potential problems arising from poor glucose regulation
• Discuss how eating and fasting affect blood sugar, and how the
body responds
Fact
• Blood glucose must be tightly regulated
• Normally, insulin and glucagon work together to ensure it is
• Problems arise when this regulation fails
(Sneak preview for your 11/11 lecture)
Hyperglycemia
• Too much glucose in blood
 Often suggests malfunction in insulin pathway
• Often seen in diabetes mellitus
• Chronic hyperglycemia carries several long term effects:
 Increased risk of cardiovascular disease and stroke
 Frequent hunger, thirst, and need for urination
 Tissue damage (e.g., retinopathy, nephropathy, neuropathy)
 Ketoacidosis
Hypoglycemia
• Too little glucose in blood
• A number of potential causes:
 Improper insulin dosage in diabetes patients
 Oversecretion of bodily insulin
 Long-term fasting
 Liver dysfunction due to alcohol
• Body responds via glucagon and epinephrine
• This is a medical emergency
The Brain.
Most researchers agree: it is important.
 CNS requires continuous supply of glucose
 Even brief denial of glucose to brain can cause long-term damage
Overview: Learning Objectives
Assuming I know what I’m doing up here, students should ultimately
be able to:
• Discuss the actions of insulin and glucagon
• Discuss the mechanisms that regulate secretion of insulin and
glucagon
• Discuss potential problems arising from poor glucose regulation
• Discuss how eating and fasting affect blood sugar, and how the
body responds
Feeding, Fasting, and Blood Sugar
• Feeding: Consuming a meal
 Breakdown of carbs = sharp increase in blood glucose
 Body responds with insulin
 Glucagon inhibited (unless meal is predominantly protein)
• Fasting: Skipping a meal, or otherwise refraining from eating




Glucose steadily falling
Insulin falls, glucagon/epinephrine rise
Body calls upon storage to meet energy demands
Fun fact: typical 70kg man has about 135,000 calories stored as fat
Feed/Fast Cycle Summarized
The key is that insulin and glucagon
work in tandem to maintain blood
glucose levels in response to food
intake, or lack thereof.
Overview: Learning Objectives
Assuming I know what I’m doing up here, students should ultimately
be able to:
• Discuss the actions of insulin and glucagon
• Discuss the mechanisms that regulate secretion of insulin and
glucagon
• Discuss potential problems arising from poor glucose regulation
• Discuss how eating and fasting affect blood sugar, and how the
body responds
My Personal Takeaway
• The human body is elegantly designed to control many physiological
parameters essential for its survival.
• At the very least, I hope you take away some appreciation for the
incredible capabilities of our physiology.
• Regardless, thank you for your attention and have a good week.
“Well that sure was fun. But hey everyone, make sure you come on
back on November 11th for a fascinating presentation on diabetes.”
-Wilford Brimley