Insulin Secretion

Question 1

Normal blood glucose levels

Answer 1

4-7mmol/L

Question 2

Alpha cells

Answer 2

glucagon

Question 3

Beta cells

Answer 3

insulin

Question 4

Blood glucose levels - regulation by insulin and glucagon

Answer 4

Glucagon increases blood glucose conc., insulin decreases blood glucose conc.

Question 5

Exocrine function of pancreas

Answer 5

Attached to duodenum and secretes digestive enzymes. Pancreas sits behind stomach.

Question 6

Islets of Langerhans

Answer 6

Alpha (mostly on the periphery) and beta cells (mostly in the middle) and digestive enzymes

Question 7

How does insulin act on fat (Adipose tissue)?

Answer 7

inhibits lipolysis - stops the breakdown and release of fat. Promotes lipogenesis

Question 8

How does insulin act on the liver?

Answer 8

Prevent glucose production

Question 9

How does insulin act on muscles?

Answer 9

Promote glucose uptake from your muscle

Question 10

3 main tissues insulin acts on

Answer 10

adipose tissue, liver, muscle

Question 11

What does the liver do and muscle doesn’t?

Answer 11

Liver’s the only tissue that will release glucose again into the bloodstream. Muscles can only store as glycogen to release glucose when exercising, but they won’t release in back to the bloodstream for other tissues to use

Question 12

glucagon’s main actions

Answer 12

increase the levels of glucose in the bloodstream. Mostly acts on the liver. Breakdown of glycogen (stored glucose) and release into the bloodstream.

Question 13

what happens after eating?

Answer 13

spike in blood glucose levels (increase). pancreas detects this, beta cells release insulin.

Question 14

insulin receptor (structure)

Answer 14

heterotetrameric structure consisting of 2 alpha subunits on outside of plasma membrane and 2 transmembrane beta subunits.

Question 15

What happens when insulin binds to its receptor?

Answer 15

Insulin binds to the alpha subunits, brings the beta subunits together in close proximity - beta subunits get activated and auto-phosphorylate on their tyrosine residues

Question 16

Upon activation of the insulin receptor…

Answer 16

Activation and phosphorylation of beta subunits of the insulin receptor leads to the activation and phosphorylation IRS1/2

Question 17

IRS1/2

Answer 17

insulin receptor substrate (isoforms 1/2)

Question 18

What regulates the phosphorylation and activation of IRS1/2?

Answer 18

PTEN - phosphatase and tensin homolog. Dephosphorylates IRS as it’s a protein tyrosine phosphatase.

Question 19

PI3K

Answer 19

PI3K binds to IRS though its p85 subunit. Once activated, phosphorylates PIP2 to PIP3. PIP3 is also dephosphorylated and negatively regulated by PTEN.

Question 20

PIP3 levels increase…

Answer 20

recruits PDK1 and Akt to the plasma membrane. PIP3 activates PDK1, which then phosphorylates Akt.

Question 21

What does Akt do to AS160 in insulin-sensitive cells?

Answer 21

Phosphorylates and inactivates AS160 (which previously downregulates the translocation of vesicles containing GLUT4 to the plasma membrane). Inactivation of AS160 leads to the translocation of this vesicle, allowing GLUT4 to embed into the membrane.

Question 22

What does GLUT4 do?

Answer 22

Upon insulin binding to its receptor and activation of the downstram signalling pathway, GLUT4 becomes embedded in the plasma membrane, allowing glucose to enter the cell, which will then undergo glycolysis.

Question 23

Role of Akt in insulin-sensitive cells (regarding GS).

Answer 23

Inactivates GSK3, which typically phosphorylates and inactivates GS (glycogen synthase). Inhibiting an inhibitor –> Akt activation leads to activating GS for glycogen synthesis to store glucose within the cell.

Question 24

Main roles of Akt (also known as PKB) in insulin-sensitive cells?

Answer 24

Glucose entry through GLUT4 for glycolysis.
Glycogen synthesis.
Increase lipogenesis.
decreasing gluconeogenesis in liver.
Negative feedback by activating mTORC1 which leads to the inhibition of IRS.

Question 25

Role of Akt in insulin-sensitive cells (regarding mTORC1).

Answer 25

Activates mTORC1 through multiple steps. mTORC1 activation leads to the activation of p70S6K, which then phosphorylates and inactivates IRS1/2. NEGATIVE FEEDBACK.

Question 26

What happens when insulin is released from its receptor?

Answer 26

GLUT4 localisation to the plasma membrane is dependent on the activation of the insulin receptor, SO after the release of insulin, GLUT4 is taken back into a vesicle

Question 27

Where does glucagon act?

Answer 27

acts on liver via glucagon receptors (GPCR) to increase cAMP and PKA.

Question 28

Action of glucagon…

Answer 28

Inhibits glycolysis and glycogenesis (i.e. decreases glycogen production) and stimulates gluconeogenesis and glycogenolysis (i.e. increase glucose production). –> more free glucose to be released in the bloodstream for other tissues

Question 29

What else can change your blood pressure?

Answer 29

exercise - using glucose so blood glucose levels might fall (muscles uptake glucose independently to insulin when exercising).
illness
stress - cortisol