Lecture 5: Insulin and glucagon action

Question 1

In what form is carbohydrates transported in the body

Answer 1

In the form of glucose

Question 2

What is the effect of insulin of glucose homeostasis

Answer 2

• Upregulates glycogenesis in the liver and muscle
• Upregulates the synthesis of fatty acids and triglycerides
• Downregulates gluconeogenesis (in the liver)

Question 3

What is the effect of glucagon on glucose homeostasis

Answer 3

• Upregulates glycogenolysis
• Upregulates gluconeogenesis
• Downregulates glycogenesis

Question 4

What is the role of the glycogen stored in the liver

Answer 4

Storage for blood glucose maintainenace

Stored when blood glucose levels are high so when levels are low they can be broken down to maintain blood glucose level

Question 5

What is the role of the glycogen stored in the muscle

Answer 5

Storage for local energy production (only used by the muscle itself)

When the glycogen is broken down it cannot go back to glucose but used for ATP because the muscle cells do not contain the enzyme G6Pase (which converts G6P to glucose)

Question 6

What happens to liver glycogen metabolism in the fed state

Answer 6

Insulin increases glucokinase and glycogen synthase activity

Increase glucokinase activity- conversion from glucose to G6P

Increase glucogen synthase activity- therefore more glycogen formed.

Question 7

What is the effect of nor(adrenaline) on muscle glycogen metabolism, if person is in a fasted state?

Answer 7

• More glucose is needed as the body is in the “fight or flight” response
• Increase GLUT4 activity (to bring glucose into the muscle cell)
• Increase hexokinase activity
• Increase glycogen phosphorylase activity (breaking down glycogen into G1P)

Question 8

Gluconeogenesis occurs where?

Answer 8

Mainly in the liver

Kidneys can contribute with prolonger starvation

Question 9

How does glyconeogenesis convert glucose-6-phosphate to glucose?

Answer 9

By glucose-6-phosphatase

Question 10

How does glyconeogenesis convert fructose-1,6-bisphosphate to fructose-6-phosphate?

Answer 10

By Fructose 1,6-bisphosphatase (F16bPase)

Question 11

How does glyconeogenesis bypass pyruvate kinase activity?

Answer 11

Converts pyruvate into oxaloacetate (by pyruvate carboxylase (PCOX))

Oxaloacetate is converted to phosphoenolpyruvate (by phosphoenolpyruvate (PEPCK))

Question 12

Draw the steps for gluconeogenesis from a pyruvate source

Answer 12

Question 13

Which hormones regulate gluconeogenesis

Answer 13

Glucagon - Increase gluconeogenesis

Adrenaline - Increase gluconeogenesis

Insulin - Decrease gluconeogenesis

Question 14

What effect does glucagon and adrenaline have on gluconeogenesis

Answer 14

Upregulates gluconeogenesis by:

• Decreasing glucokinase activity
• Increasing G6Pase and PEPCK activity

Question 15

What effect does insulin have on gluconeogenesis

Answer 15

Downregulates gluconeogenesis by:

• Increase glucokinase activity
• Decrease G6Pase and PEPCK activity

Question 16

Glucagon ____ glucokinase activity and ____ G6Pase and PEPCk activity. Overall ___regulates gluconeogenesis

Answer 16

A) Decrease

B) Increase

C) Upregulates

Question 17

Adrenaline ____ glucokinase activity and ____ G6Pase and PEPCK activity. Overall ___regulates gluconeogenesis

Answer 17

A) Decrease

B) Increase

C) Upregulates

Question 18

Insulin ____ glucokinase activity and ____ G6Pase and PEPCK activity. Overall ___regulates gluconeogenesis

Answer 18

A) Increase

B) Decrease

C) Downregulates

Question 19

At what level does hormonal regulation have on gluconeogenesis?

Answer 19

Gene level

The effect of the hormones (glucagon, adrenaline and insulin) effect the level of gene expression

Influences if more/less enzyme are synthesised- however takes a while for the effect to be influence on gluconeogenesis

Question 20

What is the principal action of insulin on the liver

Answer 20

• Increases glycogen synthesis
• Increases fatty acid synthesis
• Inhibits gluconeogenesis (PEPCK & G6Pase)

Question 21

What is the principal action of insulin on the muscle

Answer 21

• Increases glucose transport (GLUT4)
• Increases glycogen synthesis

Question 22

What is the principal action of insulin on the adipose

Answer 22

• Increases glucose transport (GLUT4)
• Suppresses lipolysis
• Increases fatty acid synthesis

Question 23

Name the hypogylcaemic drugs available

Answer 23

• Sulphonylureas
• Biguanides
• Thiazolidinediones
• Incretin mimics & DPP-4 inhibitors
• SGLT2 inhibitors

Question 24

Describe the mechanism of action for sulphonylureas + an example

Answer 24

• Hypoglycaemic drug
• Inhibits ATP-sensitive potassium channels (similar action as to the high levels of glucose, which stimulates ATP production)
• This depolarises the cells causing voltage gated calcium channels to open causing the exocytosis of insulin
• Example: Gliclazide

Question 25

Describe the mechanism of action for biguanides + an example

Answer 25

* Hypoglycaemic drug * Mechanism is uncertain- thought to inhibit mitochondrial glycerophasphate dehydrogenase in liver and activates AMPK * Mimics insulin by inhibiting hepatic gluconeogenesis (downregulating the conversion from glycogen to glucose) * Example is metformin

Question 26

Which hypoglycaemic drug makes you fat and why?

Answer 26

* Thiazolidinediones * As its stops the inappropriate deposition of lipid in non-adipose tissue. Therefore, more lipids are deposited in adipose tissues making you "fatter" * This drug improves insulin sensitivity

Question 27

Describe the incretin effect

Answer 27

Defined as the increased stimulation of insulin secretion elicited by oral as compared with intravenous administration of glucose under similar plasma glucose levels. This is because the release of gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). They stimulate the β cells- to secrete insulin. If glucose is given IV, they do not cause the release of GIP and GLP-1. As a result, these hormones do not enhance the insulin activity

Question 28

What are the incretins?

Answer 28

They are the GI hormones that potentiate insulin secretion These include: –Glucagon-like peptide-1 (GLP-1) –Gastric inhibitory peptide (GIP). –Rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).

Question 29

What is the mechanism of action for exenatide

Answer 29

Mimic increatins (GLP-1) which improves insulin secretion

Question 30

What is the mechanism of action of sidagliptin?

Answer 30

Oral hypoglycemics Block the enzyme dipeptidyl peptidase-4 (DPP-4) DPP-4 causes the breakdown of incretins, therefore sidagliptin inhibits this breakdown. Improving insulin secretion

Question 31

Describe how SGLT2 inhibitors can be used to treat type 2 diabetes + Example

Answer 31

Inhibits sodium-glucose transport protein 2 (SGLT2) Inhibits renal reuptake of glucose from filtrate Reduces hyperglycaemia Example: empagliflozin

Question 32

Increatins are rapidly inactivated by which enzyme?

Answer 32

Dipeptidyl peptidase-4 (DPP-4).