Regulation of Glucose

Question 1

What happens to glucose in the fed state and fasting state?

Answer 1

Fed state - excess glucose is stored as glycogen

Fasting state - mobilized

Question 2

What is an important contributor of glucose in the fasting state?

Answer 2

Gluconeogenesis (liver)

Question 3

What is insulin and where is it secreted?

Answer 3

Insulin is a peptide hormone secreted from the beta cells of the pancreas.

Question 4

What triggers the release of insulin?

Answer 4

Secretion triggered by entry and metabolism of glucose into pancreatic beta cells.

Question 5

Describe how glucose is released.

Answer 5

When concentration outside cell is higher than 5.5 mol
Entry via GLUT-2 and metabolism of glucose into beta cells (pancreas)
Subsequent increase in ADP/ATP
Tiggers calcium influx and activation of proteins involved in trafficking of sensory granules
Sensory granules release insulin

Question 6

Describe the formation/previous forms of insulin.

Answer 6

Preproinsulin - how insulin starts out.
Preproinsulin changes to proinsulin and signal peptide (secretory signal is clipped off)
Cleavage of C peptide changes to C-peptide and insulin

Question 7

What is important to note about C-peptide in the clinical setting?

Answer 7

C-peptide levels show you how much insulin a patient is producing
When insulin is injected, the C-peptide is removed
Therefore C-peptide levels are purely endogenous

Question 8

What do the alpha cells of the pancreas produce?

Answer 8

Glucagon

Question 9

What do the beta cells of the pancreas produce?

Answer 9

Insulin

Question 10

What do the delta cells of the pancreas produce?

Answer 10

Somatostatin

Question 11

What type of receptor is an insulin receptor?

Answer 11

Tyrosine kinase receptor - an enzyme that phosphorylates particular tyrosines found on its substrates (adds phosphate to tyrosine on proteins)

Question 12

How are the effects of insulin mediated?

Answer 12

Through an intracellular signalling cascade that either changes phosphorylation status or alters transcription or alters transcription of several enzymes involved in fuel metabolism

Question 13

Describe the general effects insulin has on the liver, muscle and fat cells.

Answer 13

Fat - lipogenesis
Muscle - glycogen synthesis (glycogenesis)
Liver - lipogenesis and glycogen synthesis (glycogenesis)

Question 14

What stimulates/inhibits and potentiates insulin secretion from B cells?

Answer 14

Stimulates - glucose >5mmol/L, arginine, alanine, glycine
Inhibits - adrenaline, glucagon
Potentiated by hormones e.g. cholecystokinin and other gut hormones (incretins)

Question 15

What is the incretin effect?

Answer 15

Delivery of oral glucose to the small intestine gives a higher insulin response than IV glucose

Question 16

What are incretins?

Answer 16

Gut hormones that help control blood glucose levels
Some stimulate insulin release
Some alter nutrient absorbance rate from the gut
Some affect appetite

Question 17

List examples of incretins.

Answer 17

Glucagon-like peptide 1 (GLP-1)

Gastric inhibitory peptide (GIP)

Question 18

List the insulin effect on fuel metabolism.

Answer 18

• Promote glucose uptake by activating GLUT4 in muscle and adipose
• Promotes glycogen synthesis (liver, muscle) and lipogenesis (liver, adipose)
• Promote glucose utilization (glycolysis - breaks down glucose)
• Inhibits gluconeogenesis (liver) and glycogenolysis (liver and muscle) & lipolysis (adipose)
• Stimulates LPL activity to promote fatty acid reuptake by adipose. Inhibits hormone sensitive lipase (breaks down fats)
• Promotes amino acid uptake

Question 19

What is the difference between GLUT 2 and GLUT 4

Answer 19

GLUT 4 - insulin sensitive (muscle and adipose)

GLUT 2 - glucose sensitive (liver)

Question 20

What effects does insulin have on the liver?

Answer 20

Increase glycogen synthesis
Increase lipogenesis
Decrease gluconeogenesis

Question 21

What effects does insulin have on the muscle?

Answer 21

Increase glucose uptake

Increase glycogen synthesis

Question 22

What effect does insulin have on the adipose tissue?

Answer 22

Increase glucose uptake
Increase lipoprotein lipase
Increase TAG storage
Decrease lipolysis

Question 23

What effect does insulin have on the pancreas?

Answer 23

Alpha cells - decrease glucagon synthesis

Question 24

Describe the regulation of glycogen synthase in the fed state?

Answer 24

Activated by insulin
- Promotes dephosphorylation by activating phosphatase, PP1 that converts glycogen synthase enzyme to its dephosphorylated form
Activated by glucose, glucose-6-phosphate