Session 7: Endocrine Pancreas

Question 1

Where does the endocrine function of the pancreas take place?

Answer 1

In the islets of langerhans

Question 2

What are the predominant cells in the islets of langerhans?

Answer 2

Alpha (20%) and beta cells (75%)

Question 3

Ultrastructure of alpha and beta cells of the islets of langerhans.

Answer 3

Extensive rough ER Well-defined Golgi Extensive mitochondria Well-defined system of microtubules and microfilaments

Question 4

Structure of insulin

Answer 4

Polypeptide hormone containing two polypeptide chains One A chain and one B chain (not alpha and beta) The A and B chains are linked together by disulphide bridges (two in total) There is also a third disulphide bond which is intra-chain on the A chain.

Question 5

Explain synthesis of insulin

Answer 5

Synthesised as pre-proinsulin on ribosomes on rough ER. Pre-part is a signal peptide that makes the protein enter the cisternal space of the ER. Signal peptide Is removed and pro-insulin remains. Pro-insulin folds and ensures correct alignment of cysteine residues and correct disulphide bonds. Proinsulin goes to trans-Golgi and is packaged into vesicles. Once in the vesicles and in the golgi proteolysis occurs. C-peptide is removed the once uni-strandular protein becomes two strands. One A-chain and one B-chain, this is the final product of insulin.

Question 6

Where is insulin then stored?

Answer 6

In beta-cell storage granules as a crystalline zinc-complex.

Question 7

Is there anything else in the storage-granules that hold the insulin?

Answer 7

C-peptide are still left in the granules. The C-peptide to insulin ratio will be 1:1. Also there will be some pro-insulin left. This means that C-peptide will be released once insulin is released on stimulus.

Question 8

Why is C-peptide important?

Answer 8

The mechanism of action of active C-peptides are unknown and also what they do. However the C-peptide levels in blood can be used to measure the endogenous insulin production of patients given insulin. What this means is that the insulin to C-peptide ratio will not be the same anymore. The C-peptide levels will therefore show how much insulin is released by the body’s own pancreas.

Question 9

In the blood stream, how is insulin transported?

Answer 9

Since it is a water-soluble hormone it is transported as a free hormone not bound to any transport protein.

Question 10

What are the target tissues of insulin?

Answer 10

Mainly the liver, skeletal muscle and adipose.

Question 11

What are the target tissues of glucagon?

Answer 11

Mainly the liver and adipose tissue.

Question 12

What type of receptor does insulin act on?

Answer 12

Tyrosine-kinase receptor family

Question 13

What are the short term actions of insulin?

Answer 13

Anabolic effects like absorption of nutrients after a meal.

Question 14

What are the long term actions of insulin?

Answer 14

Affects cell growth and division that relate to its ability to stimulate the synthesis of new protein molecules and to stimulate DNA replication.

Question 15

What are the major actions of insulin on carbohydrate, lipid and amino acid metabolism?

Answer 15

Increased glucose transport into adipose tissue and skeletal muscle Increased glycogenesis and decreased glycogenesis in liver and muscle Decreased gluconeogenesisin liver Increased glycolysis in liver and adipose tissue Decrease lipolysis in adipose tissue Increased lipogenesis and esterification of fatty acids in liver and adipose tissue Decreased ketogenesis in liver Increased lipoprotein lipase activity Increased amino acid uptake and protein synthesis in liver Decreased proteolysis in liver, skeletal muscle and heart muscle.

Question 16

How is the rate of secretion of insulin controlled?

Answer 16

Metabolites like glucose, amino acids and fatty acids

GI-tract hormones like gastrin, secretin and cholecystokinin

Neurotransmitters like adrenalin, noradrenaline and acetylcholine.

Question 17

Of the above mentioned. What will increase and what will decrease the rate of secretion of insulin?

Answer 17

Question 18

Structure of glucagon.

Answer 18

Single chain, 29 amino acid peptide hormone.

No disulphide bonds

Question 19

Synthesis of glucagon.

Answer 19

By pancreatic alpha cells as a larger precursor molecule called pre-proglucagon which will undergo post-translational processing to produce the biologically active molecule.

Question 20

Main actions of glucagon.

Answer 20

Question 21

Mechanism of action of glucagon.

Answer 21

Binds to GPCR on cell surface of target cells (predominantly liver and adipose tissue)

Activation of adenylyl cyclase

Increase of cAMP

Activation of protein kinase A

Phosphorylation of important enzymes

Question 22

What are the major factors that impact the rate of glucagon secretion?

Answer 22

Increase:

A decrease in blood glucose conc.

Decrease:

Inhibition by insulin and an increase in blood glucose conc.