Session 10 Lecture 1

Question 1

Is the pancreas an exocrine or endocrine organ?

Answer 1

BOTH

Question 2

What are the functions of the pancreas?

Answer 2

• Exocrine

- Endocrine

Question 3

What is the exocrine function of the pancreas?

Answer 3

Produced digestive enzymes secreted directly into duodenum.

Question 4

What is the endocrine function of the pancreas?

Answer 4

Hormone production from the islets of langerhans

Question 5

What percentage of pancreas is exocrine and what percentage is endocrine?

Answer 5

1% endocrine tissue

99% exocrine tissue

Question 6

What is the embryological development of the pancreas like?

Answer 6

Develops embryologically as an outgrowth of the foregut

Question 7

Name some important polypeptide hormones secreted by the pancreas?

Answer 7

Insulin, glucagon, somatostatin, ghrelin, gastrin etc

Question 8

What are the major cell types found in islets?

Answer 8

Beta cells ~ 75%

Alpha cells ~ 20%

Question 9

What do the beta cells of the islets of langerhans produce?

Answer 9

Insulin

Question 10

What do the alpha cells of the islets of langerhans produce?

Answer 10

Glucagon

Question 11

What type of hormone is insulin?

Answer 11

Peptide hormone

Question 12

Describe this structure of insulin

Answer 12

Two polypeptide chains (a and B chains) linked covalent by two disulfide bonds. There is also a 3rd intra-chain disulfide bond within chain A. Rigid structure

Question 13

Describe some of the properties of insulin?

Answer 13

Water soluble hormone
Carried dissolved in plasma - no protein
Short half life
Interact with cell surface rectors

Question 14

Briefly describe the synthesis of insulin

Answer 14

Synthesised as pre-proinsulin on ribosomes associated with the RER. Once it enters the ER, the signal is removed. The proinsulin folds to ensure that there is correct alignment of the cysteine residues and correct disulfide bond formation. Proinsulin is moved from the ER to the golgi and packed into storage vesicles. In the vesicle proteolysis removes C-peptide and this breaks the single chains into two chains that are held together by a disulfide bridges - mature insulin and C peptide. The two products are released from the vesicle in equimolar amounts.

Question 15

Why is there a “pre” part to proinsulin?

Answer 15

The ‘pre’ part ensures that the newly synthesised protein enters the cistern all space of the ER.

Question 16

What can a measurement of C-protein be sued for?

Answer 16

Used in patients receiving insulin to monitor any endogenous insulin secretion

Question 17

How is insulin stored?

Answer 17

Stored in a B-cell storage granule as a crystalline zinc-insulin complex.

Question 18

Does insulin need to be bound to a protein when in the blood?

Answer 18

No - it is a free hormone

Question 19

What are the major target for insulin?

Answer 19

Liver, skeletal muscle and adipose tissue

Question 20

What family is the insulin receptor part of?

Answer 20

Tyrosine Kinase receptor family

Question 21

Describe the structure of the insulin receptor?

Answer 21

Receptor is a diner, two identical subunits spanning the cell membrane. Two subunits are made of one alpha chain and one beta chain connected by a disulfide bond.

Question 22

What part of the insulin receptor is on the exterior of the cell membrane?

Answer 22

Alpha chain is on the exterior

Beta chain spans the cell membrane

Question 23

What does insulin do?

Answer 23

Increases glucose uptake into target cells and glycogen synthesis - GLUT 4 channel

Question 24

Function of insulin in the liver?

Answer 24

Increases glycogen synthesis by stimulating glycogen formation and by inhibiting breakdown

Question 25

Insulin function in muscle?

Answer 25

Increase intake of AA promoting protein synthesis

Question 26

Action of insulin in adipose tissue?

Answer 26

Increases the storage of triglycerides

Question 27

Why does insulin secretion need to be controlled?

Answer 27

Insulin acts to lower blood glucose concentration therefore need to control it to make sure insulin stays in normal physiological range

Question 28

What stimulates insulin secretion?

Answer 28

Metabolic signals, GI tract hormones and acetylcholine

Question 29

What inhibits the section of insulin?

Answer 29

Adrenaline and noradrenaline

Question 30

What are K ATP channels?

Answer 30

Type of potassium channel that is gated by intracellular nucleotides - ADP and ATP.

Question 31

Describe the structure of glucagon

Answer 31

Single chain - the molecule lacks disulfide bonds and has a flexible structure.

Question 32

Briefly describe the synthesis of glucagon

Answer 32

Synthesised by pancreatic alpha cells as precursor molecules pre-proglucagon that undergoes post-translational processing to produce the biologically active molecule.

Question 33

What are the actions of glucagon in the liver?

Answer 33

Increase glycogenolysis and decrease glycogenesis. Increase glucogneogensis and ketogenesis

Question 34

What are the actions of glucagon in the adipose tissue?

Answer 34

Increased lipolysis

Question 35

Describe the mechanism of action of glucagon?

Answer 35

Glucagon binds to GPCR. This activates enzyme adenylate cyclase which increase cAMP which activates PKA. This phosphorylates and thereby activates a number of important enzymes.

Question 36

What increases the secretion of glucagon?

Answer 36

Decreased blood glucose concentration

Question 37

What inhibits the secretion of glucagon?

Answer 37

Insulin and increased blood glucose concentration