Endocrine Pancreas

Question 1

Type 1 diabetes occurs due to…

Answer 1

Autoimmune destruction of beta cells

This leads to insulin deficiency

Question 2

Type 2 diabetes occurs due to…

Answer 2

Insulin resistance + beta cell dysfunction

This leads to relative insulin deficiency

Question 3

The endocrine cells of the pancreas are found in clusters known as…

Answer 3

The Islets of Langerhans

Question 4

What % of pancreatic volume is made up of the islets of langerhans?

Answer 4

1-2%

The rest is exocrine acinar cells which secrete digestive juices

Question 5

List 5 different islet cell types and what they secrete

Answer 5

Alpha cells -> glucagon

Beta cells -> insulin

Delta cells -> somatostatin

PP cells -> pancreatic polypeptide

Epsilon cells -> ghrelin

Question 6

Roughly what proportion of the pancreatic islets are alpha, beta, delta and PP cells?

Answer 6

Beta - 55%
Alpha - 38%
Delta - <5%
PP - ~1%

Question 7

At what blood glucose threshold is insulin released?

Answer 7

When BG >5.5 mmol/L

Question 8

At what blood glucose threshold is glucagon released?

Answer 8

When BG <4 mmol/L

Question 9

Describe regulation of glucose homeostasis by insulin

Answer 9

• Hyperglycaemia and hyperlipidaemia occur during feeding
• Pancreatic beta cells release insulin when glucose >5.5 mmol/L
• Glycogen synthesis and lipid storage occur due to uptake of glucose into the liver, muscle and fat
• Blood glucose and lipid levels drop back to normal

Question 10

Beta cells are switched off at low glucose levels. T/F

Answer 10

True

And alpha cells are switched off at high glucose levels

Question 11

Describe regulation of glucose homeostasis by glucagon

Answer 11

• Hypoglycaemia and hypolipidaemia occur during fasting/exercise
• Pancreatic alpha cells release glucagon when glucose <4 mmol/L
• Glycogen breakdown and lipolysis occur
• Blood glucose and lipid levels raise back to normal

Question 12

In T2DM, beta cell mass in the pancreas decreases, suggesting that…

Answer 12

Beta cells are lost or dedifferentiate

Question 13

When insulin resistance first develops, why does T2DM not immediately occur?

When does T2DM occur?

Answer 13

Beta cells release more insulin to compensate

T2DM occurs when beta cells fail to produce enough insulin to meet demands

Question 14

Describe how glucose binds to beta cells and causes insulin release

Answer 14

• Glucose taken in by GLUT 2 transporters
• Glucokinase converts it to glucose-6-phosphate which is used in glycolysis, the TCA cycle and oxidative phosphorylation to produce ATP
• ATP binds to ATP sensitive K+ channels, causing them to close
• K+ builds up in the cell, depolarising the membrane
• Ca2+ can enter through voltage gated Ca2+ channels
• Ca2+ triggers insulin granule exocytosis

Question 15

Insulin secretion often loses its biphasic nature in type 1 diabetes. T/F

Answer 15

False

Insulin secretion often loses its biphasic nature in type 2 diabetes

Insulin is not secreted in type 1 diabetes

Question 16

Besides glucose, what other molecules do beta cells regulate insulin in response to?

Answer 16

Nutrients e.g., free fatty acids, amino acids

Hormones e.g., leptin, adiponectin, IGF1, glucagon

Neurotransmitters e.g., acetylcholine

Question 17

Describe how hypoglycaemia causes glucagon release from alpha cells

Answer 17

• Glucose uptake and metabolism is low so KATP channels open
• K+ leaves the cell
• Voltage gated Na+ channels (NaV) open, allowing Na+ to enter the cell
• This triggers action potentials that open P/Q type voltage gated Ca2+ channels (CaV)
• Ca2+ entry triggers glucagon granule exocytosis

Question 18

Where does glucagon have its biggest effect once it is released? What does it do here?

Answer 18

In the liver

Glucagon stimulates hepatic glucose output by promoting glycogen breakdown

It also stimulates gluconeogenesis

Question 19

What alpha cell defect may be seen contributing to hyperglycaemia in T2DM?

Answer 19

Glucagon may still be released in the fed state which means that hepatic glucose production is still being stimulated

This contributes to hyperglycaemia

Question 20

Define an exocrine cell in relation to the pancreas

Answer 20

A cell which secretes digestive juices into the ducts which drain into the gut

Question 21

Define an endocrine cell in relation to the pancreas

Answer 21

A cell which secretes hormones into the blood stream which then travel to distal target organs

Question 22

Define a paracrine cell

Answer 22

A cell which releases a soluble factor which then influences adjacent cells

Question 23

Define an autocrine cell

Answer 23

A cell which releases a soluble factor which binds to a receptor on that same cell

Question 24

Define a juxtacrine cell

Answer 24

A cell which presents a ligand on its surface which will interact with the cell next to it

Question 25

Describe the paracrine action of delta cells

Answer 25

Delta cells secrete somatostatin 14 which suppresses beta and alpha cell function in a paracrine manner

Question 26

Delta cells release SST14 in response to...

Answer 26

Nutrients, hormones and neurotransmitter stimulation

Question 27

How does somatostatin 14 suppress alpha and beta cells?

Answer 27

It binds to G-protein coupled receptors which are coupled to Gi (inhibitory) proteins This inhibits cAMP production

Question 28

Why are delta cells good at suppressing multiple alpha and beta cells at a time?

Answer 28

They have an unusual neuron-like shape that allows them to be in contact with multiple cells

Question 29

What is meant by the incretin effect?

Answer 29

Insulin secretion is greater in response to oral glucose in comparison with IV glucose infusion

Question 30

What are incretins?

Answer 30

Hormones released from the gut which stimulate insulin release in response to oral glucose (i.e., glucose dependent)

Question 31

What is the main incretin hormone?

Answer 31

Glucagon-like peptide 1 (GLP1)

Question 32

GLP1 incretin hormone is released from ? cells in the small and large intestines

Answer 32

L-cells

Question 33

Which enzyme is responsible for the breakdown of incretins?

Answer 33

DPP4

Question 34

When might a DPP4 inhibitor be used?

Answer 34

To increase release of insulin for treatment of hyperglycaemia in T2DM (as less incretins are being broken down so more are available to stimulate insulin release)