1. Pancreas and glucose
By Juliana Xie

2. Pan-creas! Greek: “pan” = all; “creas” = flesh
Pancreas is like a fish! Head, body, and tail.
Important anatomical relationships

3. 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

4. What makes the pancreas such an important organ?
Outline pancreatic gross and cellular anatomy
Discuss the normal function of the pancreas in glucose metabolism

5. Pancreas: two major roles
2) Endocrine
Produce enzymes that CHOP (digest) food
Control the sugar levels in the body
1) Exocrine

6. 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

7. A closer look: Endocrine Pancreatic cells
Alpha cells  glucagon
Beta cells  insulin
Gamma cells  pancreatic polypeptide
Delta cells  somatostatin
Observe how these cells lie in close proximity of capillaries.

8. 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 1000-fold overproduction of glucagon
-blood glucose raises via gluconeogenesis and lipolysis
-causes diabetes mellitus

9. 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

10. 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

11. 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.

12. Pancreas and Glucose Homeostasis
Glucose regulation works in a system of organs

13. Pancreas and Glucose Homeostasis

14. 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

15. Hormonal Regulation of Glucose Metabolism
Luke D. Piper

16. 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

17. 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
Glucagon
Both

18. Insulin Polypeptide hormone Produced in the Pancreas
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

19. 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

20. Insulin Action: Visual Aid
Recall: insulin is anabolic

21. 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

22. 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.

23. 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

24. 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.

25. Glucagon Regulation Glucagon secretion is stimulated by:
Low blood glucose
Amino acid ingestion
Epinephrine
Glucagon secretion is inhibited by:
High blood glucose
Insulin

26. 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)

27. 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

28. Fact Blood glucose must be tightly regulated
Normally, insulin and glucagon work together to ensure it is
Problems arise when this regulation fails

29. Hyperglycemia Too much glucose in blood
(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

30. Most researchers agree: it is important.
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
CNS requires continuous supply of glucose
Even brief denial of glucose to brain can cause long-term damage
The Brain.
Most researchers agree: it is important.

31. 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

32. 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

33. 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.

34. 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

35. 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