insulin and glucagon signalling

Question 1

What is the primary role of insulin in the body?

Answer 1

Insulin promotes glucose storage as glycogen and regulates blood glucose levels by enhancing glucose uptake into cells.

Question 2

Where is insulin produced?

Answer 2

Insulin is produced by the beta (B) cells in the pancreatic Islets of Langerhans.

Question 3

How is insulin synthesized?

Answer 3

Insulin is first synthesized as a polypeptide (84 amino acids), processed into pro-insulin, and activated by the removal of the C chain to form two polypeptide chains (A and B) linked by disulphide bridges.

Question 4

How does glucose induce insulin secretion?

Answer 4

Elevated glucose levels lead to ATP generation, closing ATP-sensitive K+ channels, causing depolarization, which opens voltage-gated Ca2+ channels, triggering insulin release from secretory granules.

Question 5

What are the two phases of insulin secretion?

Answer 5

The first phase involves the release of stored insulin, and the second phase involves synthesis and secretion of new insulin.

Question 6

How does insulin circulate, and what is its plasma half-life?

Answer 6

Insulin circulates in free form, with a plasma half-life of approximately 6 minutes, degraded mainly by insulinase in the liver, muscle, and kidneys.

Question 7

What is the structure of the insulin receptor?

Answer 7

The insulin receptor is a dimeric receptor composed of two subunits (α and β), which undergo dimerization and activation upon insulin binding.

Question 8

What happens after insulin binds to its receptor?

Answer 8

The receptor activates IRS-1, which then activates PI3K, leading to cellular responses like glucose uptake.

Question 9

How does insulin promote glucose uptake in liver cells?

Answer 9

Insulin activates PI3K, which activates PKB, leading to the translocation of GLUT4 to the plasma membrane, allowing glucose uptake.

Question 10

How does insulin promote glycogen synthesis?

Answer 10

Insulin activates glycogen synthase, facilitating glucose storage as glycogen in the liver and skeletal muscle.

Question 11

What happens when glycogen reserves are full?

Answer 11

Excess glucose is converted to fatty acids, which are stored as fat.

Question 12

How does insulin promote protein synthesis?

Answer 12

Insulin activates the TORC1 pathway, stimulating the incorporation of amino acids into proteins.

Question 13

How does insulin affect metabolic substrates?

Answer 13

Insulin increases glucose permeability, switching cells to use glucose instead of fatty acids for energy.

Question 14

How does insulin regulate fat storage?

Answer 14

Insulin promotes fat deposition in adipocytes and reduces the release of free fatty acids.

Question 15

Which major tissue is insulin-independent for glucose uptake?

Answer 15

The brain’s CNS cells uptake glucose independently of insulin.

Question 16

What is the primary role of glucagon?

Answer 16

Glucagon opposes insulin by raising blood glucose levels, promoting glycogen breakdown, and gluconeogenesis.

Question 16

Where is glucagon produced?

Answer 16

Glucagon is produced by alpha (A) cells in the pancreatic Islets of Langerhans.

Question 17

What triggers glucagon secretion?

Answer 17

Hypoglycaemia is the major trigger, while hyperglycaemia suppresses glucagon secretion.

Question 18

How does glucagon affect blood glucose?

Answer 18

Glucagon has a potent hyperglycaemic action, promoting glycogenolysis and glucose release from the liver.

Question 19

What type of receptor does glucagon bind to?

Answer 19

Glucagon binds to a G protein-coupled receptor (GPCR) linked to the cAMP/PKA signalling pathway.

Question 20

What is glucagon’s role during exercise?

Answer 20

It promotes glucose release to provide extra fuel for skeletal muscle and the nervous system, despite skeletal muscles lacking glucagon receptors.

Question 21

How do amino acids affect glucagon secretion?

Answer 21

High plasma amino acid levels stimulate glucagon secretion to counteract the glucose-lowering effects of insulin.

Question 22

Why is glucagon critical during starvation?

Answer 22

Glucagon maintains blood glucose by promoting gluconeogenesis from lipids and amino acids when glycogen stores are depleted.

Question 23

How does glucagon influence lipid metabolism?

Answer 23

High glucagon levels promote fatty acid release from adipose tissue.

Question 24

How does glucagon promote glycogenolysis?

Answer 24

By activating the cAMP/PKA signalling pathway via its GPCR receptor.

Question 25

How does glucagon affect proteins during starvation?

Answer 25

It promotes protein degradation to fuel gluconeogenesis.

Question 26

What is glucagon’s main target organ?

Answer 26

The liver, where it stimulates glycogen breakdown and glucose production.

Question 27

How does glucagon ensure brain function during starvation?

Answer 27

By maintaining glucose availability through gluconeogenesis.

Question 28

How does glucagon counter insulin’s effects on fat cells?

Answer 28

By promoting the release of free fatty acids from adipose tissue.

Question 29

How do insulin and glucagon function relative to each other?

Answer 29

They function as hormonal opposites, with insulin lowering and glucagon raising blood glucose levels.

Question 30

What is the membrane potential (𝑉𝑚) of β-cells exposed to low glucose levels?

Answer 30

Approximately -65 mV (hyperpolarised).

Question 31

What happens to ATP levels in β-cells at low glucose (5 mM)?

Answer 31

ATP levels remain normal.

Question 32

Why do K+ channels stay open in β-cells exposed to low glucose?

Answer 32

Normal ATP levels do not close ATP-sensitive K+ channels.

Question 33

Are Ca2+ channels open or closed when β-cells are exposed to low glucose?

Answer 33

Closed, due to hyperpolarisation of the membrane.

Question 34

Do β-cells secrete insulin at low glucose levels (5 mM)?

Answer 34

No, insulin secretion does not occur.

Question 35

What is the membrane potential (𝑉m) of β-cells exposed to high glucose levels?

Answer 35

Approximately -25 mV (depolarised).

Question 36

What happens to ATP levels in β-cells at high glucose (10 mM)?

Answer 36

ATP levels are elevated.

Question 37

How does high glucose affect ATP-sensitive K+ channels in β-cells?

Answer 37

Elevated ATP levels close the ATP-sensitive K+ channels.

Question 38

What effect does depolarisation have on Ca2+ channels in β-cells?

Answer 38

Depolarisation opens voltage-gated Ca2+ channels.

Question 39

How do high glucose levels lead to insulin secretion in β-cells?

Answer 39

Elevated ATP closes K+ channels, causing depolarisation and opening Ca2+ channels. Ca2+ influx promotes insulin secretion from secretory vesicles.

Question 40

What are the key steps in β-cells exposed to low glucose levels (5 mM)?

Answer 40

1. Glucose enters the cell via GLUT2 (type 2 glucose transporter).
2. Normal glucose results in normal ATP levels.
3. ATP-sensitive K+ channels remain open.
4. 𝑉𝑚 is hyperpolarised (approximately -65 mV).
5. Voltage-gated Ca2+ channels stay closed.
6. β-cells do not secrete insulin.

Question 41

What are the key steps in β-cells exposed to high glucose levels (10 mM)?

Answer 41

1. Glucose enters the cell via GLUT2 (type 2 glucose transporter).
2. High glucose increases ATP levels.
3. Elevated ATP closes ATP-sensitive K+
   channels.
4. 𝑉𝑚 becomes depolarised (approximately -25 mV).
5. Voltage-gated Ca2+ channels open due to depolarisation.
6. Ca2+ influx promotes the release of insulin-containing secretory vesicles.
7. Insulin is secreted.