Endocrinology of Insulin I

Question 1

What 4 substances are produced by the islets of Langerhans in the pancreas, and by which cells?

Answer 1

1. Insulin - B cells
2. Glucagon - A cells
3. Somatostatin - Delta cells
4. Pancreatic polypeptide - F cells

Question 2

Which type of cell dominates the core of the islets of Langerhans?

Answer 2

B cells

Question 3

In which direction does blood flow in the islets of Langerhans?

Answer 3

From the core, to the periphery of the islets.

Question 4

How is the insulin peptide formed in B cells?

Answer 4

1. mRNA transcribes insulin gene, which is then translated into a functional protein
2. This is called proinsulin
3. Proinsulin is made up of A, B, C, and D peptides which are held via disulphide bridges
4. Proinsulin is then cleaved by carboxypeptidase E and forms insulin + peptide C
5. Insulin is released from secretory granules when required in the presence of Ca2+

Question 5

Which 2 transporters are responsible for glucose entering a cell?

Answer 5

GLUT 1 and GLUT 2 transporters - only found on B cells

GLUT 4 receptors are found on all cells in the body

Question 6

What is the process of insulin secretion out of a B cell?

Answer 6

1. Glucose binds to GLUT1 or GLUT2 transporter
2. It is then phosphorylated by glucokinase
3. ADP –> ATP formed via glycolysis respiration
4. An ATP-sensitive K+ channel will interact with ATP and close, blocking the efflux of K+ ions out of the channel
5. The membrane depolarises and opens voltage-gated Ca2+ channels
6. Ca2+ entry stimulates insulin secretory vesicles and release insulin via exocytosis

Question 7

What happens to glucose as insulin is secreted?

Answer 7

1. Glucose uptake increases
2. Storage of glycogen increases (glycogenesis)
3. Promotes protein/fat synthesis
4. Glycogenolysis (glycogen –> glucose) inhibited
5. Gluconeogenesis (protein –> glucose) inhibited

Question 8

What is the process which regulates the fate of glucose metabolism?

Answer 8

1. Tyrosine receptors bind to insulin
2. Insulin is phosphorylated to form IRS
3. Secondary pathways are stimulated to regulate transcription factors of enzymes
4. Enzymes are encoded which are required for the metabolism of glucose

Question 9

What factors can affect insulin release?

Answer 9

1. Glucocorticoids
2. Glucagon
3. Incretins - increase insulin release
4. Somatostatin - decreases insulin/glucagon

Question 10

How does parasympathetic stimulation affect insulin release?

Answer 10

The PNS is stimulated via the vagus nerve, which increases insulin release from B cells

Question 11

Which cells are stimulated to prevent hypoglycaemia?

Answer 11

A cells

Question 12

Where is cortisol produced?

Answer 12

In the cortex of adrenal glands in the kidneys (from cholesterol)

Question 13

What is the function of cortisol?

Answer 13

It promotes the breakdown of proteins into amino acids.

In the liver it then increases the synthesis of gluconeogenic enzymes, which can use these amino acids

Question 14

Which 2 processes do glucocorticoids (e.g. cortisol) increase in the liver?

Answer 14

Gluconeogenesis and glycogenolysis - both aim to increase blood sugar levels

Question 15

How is glucagon formed from A cells?

Answer 15

1. A peptide protein is transcribed and translated
2. A proglucagon molecule is formed
3. This is processed by prohormone convertase 2 (PC2) to then produce mature glucagon

Question 16

What 2 processes in the liver does glucagon increase?

Answer 16

Glycogenolysis and gluconeogenesis - aiming to increase blood sugar levels

Question 17

Which GLUT receptor is expressed on A cells?

Answer 17

A cells only express GLUT 1 receptors.

B cells express both GLUT 1 & GLUT 2.

Question 18

What happens to glucagon during normal or fed state?

Answer 18

Glucagon is inhibited.

Question 19

How is glucagon release from A cells inhibited during normal/fed state (high BG levels)?

Answer 19

1. At high BG levels, GLUT 1 receptors are fully saturated on A cells
2. Glucose is metabolised in glycolysis via respiration to produce ATP
3. ATP sensitive K+ channels respond to this and close
4. This blockage causes excessive membrane depolarisation, which also closes Ca2+ channels
5. This inhibits the release of glucagon in A cells

Question 20

How is glucagon released from A cells during low BG levels?

Answer 20

K+ channels close and moderately depolarise the membrane, allowing Ca2+ to open and allow the exocytosis of glucagon.

Question 21

Which incretins are released in the gut in response to feeding, and enhance insulin release by priming B cells?

Answer 21

1. GLP-1 - glucagon like intestinal peptide 1 released by L cells
2. CCK - released by I cells in the duodenum
3. GIP - gastric inhibitory peptide, released by K cells in the duodenum

Question 22

What occurs when glucose is given orally, vs IV?

Answer 22

Oral: glucose interacts with incretins to produce a massive insulin increase

IV: you bypass the GI, so incretins are not stimulated and insulin does not increase

Question 23

Which cells in the stomach and pancreas synthesise somatostatin?

Answer 23

Stomach: D cells
Pancreas: Delta cells

Question 24

What substances does somatostatin decrease the release of?

Answer 24

1. Glucagon
2. Gastrin
3. Insulin
4. Thyroid stimulating hormone (TSH)

Question 25

How is insulin secretion inhibited by somatostatin (or A agonists)?

Answer 25

Somatostatin/A agonists inhibit adenylyl cyclase, which prevents cAMP and PKA formation.
When PKA, is inhibited, insulin release is also inhibited

Question 26

How does the positioning of the cells on the islets of Langerhans allow glucagon to prevent insulin release?

Answer 26

A cells on the periphery of the islets of Langerhans release glucagon which never cross B cells, since they are located in the core of the islets.

Glucagon can therefore prevent insulin release.