insulin and glucagon signalling Flashcards
lecture 15
What is the primary role of insulin in the body?
Insulin promotes glucose storage as glycogen and regulates blood glucose levels by enhancing glucose uptake into cells.
Where is insulin produced?
Insulin is produced by the beta (B) cells in the pancreatic Islets of Langerhans.
How is insulin synthesized?
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.
How does glucose induce insulin secretion?
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.
What are the two phases of insulin secretion?
The first phase involves the release of stored insulin, and the second phase involves synthesis and secretion of new insulin.
How does insulin circulate, and what is its plasma half-life?
Insulin circulates in free form, with a plasma half-life of approximately 6 minutes, degraded mainly by insulinase in the liver, muscle, and kidneys.
What is the structure of the insulin receptor?
The insulin receptor is a dimeric receptor composed of two subunits (α and β), which undergo dimerization and activation upon insulin binding.
What happens after insulin binds to its receptor?
The receptor activates IRS-1, which then activates PI3K, leading to cellular responses like glucose uptake.
How does insulin promote glucose uptake in liver cells?
Insulin activates PI3K, which activates PKB, leading to the translocation of GLUT4 to the plasma membrane, allowing glucose uptake.
How does insulin promote glycogen synthesis?
Insulin activates glycogen synthase, facilitating glucose storage as glycogen in the liver and skeletal muscle.
What happens when glycogen reserves are full?
Excess glucose is converted to fatty acids, which are stored as fat.
How does insulin promote protein synthesis?
Insulin activates the TORC1 pathway, stimulating the incorporation of amino acids into proteins.
How does insulin affect metabolic substrates?
Insulin increases glucose permeability, switching cells to use glucose instead of fatty acids for energy.
How does insulin regulate fat storage?
Insulin promotes fat deposition in adipocytes and reduces the release of free fatty acids.
Which major tissue is insulin-independent for glucose uptake?
The brain’s CNS cells uptake glucose independently of insulin.
What is the primary role of glucagon?
Glucagon opposes insulin by raising blood glucose levels, promoting glycogen breakdown, and gluconeogenesis.
Where is glucagon produced?
Glucagon is produced by alpha (A) cells in the pancreatic Islets of Langerhans.
What triggers glucagon secretion?
Hypoglycaemia is the major trigger, while hyperglycaemia suppresses glucagon secretion.
How does glucagon affect blood glucose?
Glucagon has a potent hyperglycaemic action, promoting glycogenolysis and glucose release from the liver.
What type of receptor does glucagon bind to?
Glucagon binds to a G protein-coupled receptor (GPCR) linked to the cAMP/PKA signalling pathway.
What is glucagon’s role during exercise?
It promotes glucose release to provide extra fuel for skeletal muscle and the nervous system, despite skeletal muscles lacking glucagon receptors.
How do amino acids affect glucagon secretion?
High plasma amino acid levels stimulate glucagon secretion to counteract the glucose-lowering effects of insulin.
Why is glucagon critical during starvation?
Glucagon maintains blood glucose by promoting gluconeogenesis from lipids and amino acids when glycogen stores are depleted.
How does glucagon influence lipid metabolism?
High glucagon levels promote fatty acid release from adipose tissue.
How does glucagon promote glycogenolysis?
By activating the cAMP/PKA signalling pathway via its GPCR receptor.
How does glucagon affect proteins during starvation?
It promotes protein degradation to fuel gluconeogenesis.
What is glucagon’s main target organ?
The liver, where it stimulates glycogen breakdown and glucose production.
How does glucagon ensure brain function during starvation?
By maintaining glucose availability through gluconeogenesis.
How does glucagon counter insulin’s effects on fat cells?
By promoting the release of free fatty acids from adipose tissue.
How do insulin and glucagon function relative to each other?
They function as hormonal opposites, with insulin lowering and glucagon raising blood glucose levels.
What is the membrane potential (𝑉𝑚) of β-cells exposed to low glucose levels?
Approximately -65 mV (hyperpolarised).
What happens to ATP levels in β-cells at low glucose (5 mM)?
ATP levels remain normal.
Why do K+ channels stay open in β-cells exposed to low glucose?
Normal ATP levels do not close ATP-sensitive K+ channels.
Are Ca2+ channels open or closed when β-cells are exposed to low glucose?
Closed, due to hyperpolarisation of the membrane.
Do β-cells secrete insulin at low glucose levels (5 mM)?
No, insulin secretion does not occur.
What is the membrane potential (𝑉m) of β-cells exposed to high glucose levels?
Approximately -25 mV (depolarised).
What happens to ATP levels in β-cells at high glucose (10 mM)?
ATP levels are elevated.
How does high glucose affect ATP-sensitive K+ channels in β-cells?
Elevated ATP levels close the ATP-sensitive K+ channels.
What effect does depolarisation have on Ca2+ channels in β-cells?
Depolarisation opens voltage-gated Ca2+ channels.
How do high glucose levels lead to insulin secretion in β-cells?
Elevated ATP closes K+ channels, causing depolarisation and opening Ca2+ channels. Ca2+ influx promotes insulin secretion from secretory vesicles.
What are the key steps in β-cells exposed to low glucose levels (5 mM)?
- Glucose enters the cell via GLUT2 (type 2 glucose transporter).
- Normal glucose results in normal ATP levels.
- ATP-sensitive K+ channels remain open.
- 𝑉𝑚 is hyperpolarised (approximately -65 mV).
- Voltage-gated Ca2+ channels stay closed.
- β-cells do not secrete insulin.
What are the key steps in β-cells exposed to high glucose levels (10 mM)?
- Glucose enters the cell via GLUT2 (type 2 glucose transporter).
- High glucose increases ATP levels.
- Elevated ATP closes ATP-sensitive K+
channels. - 𝑉𝑚 becomes depolarised (approximately -25 mV).
- Voltage-gated Ca2+ channels open due to depolarisation.
- Ca2+ influx promotes the release of insulin-containing secretory vesicles.
- Insulin is secreted.
