Glucose Homeostasis Lecture

Question 1

What is the absorptive state?

Answer 1

The state during which your body is absorbing nutrients.

Question 2

What macronutrients does insulin regulate the metabolism of?

Answer 2

• Glucose
• Amino acids
• Fats

Question 3

What is the secretory functional unit of the pancreas?

Answer 3

The Islet of Langerhan

Question 4

What cells are located within Islets of Langerhans? What do they each secrete?

Answer 4

Alpha cells - Glucagon

Beta cells - Insulin

Delta cells - Somatostatin

Question 5

What is the function of the hormone somatostatin?

Answer 5

Suppresses the release of insulin and glucagon.

Question 6

What two forms of signalling occur in Islets of Langerhans?

Answer 6

Paracrine and endocrine signalling

Question 7

Is insulin anabolic or catabolic? Why?

Answer 7

Anabolic because it requires energy (and synthesises larger molecules).

Question 8

Is glucagon anabolic or catabolic? Why?

Answer 8

Catabolic because it releases energy (and breaks down larger molecules).

Question 9

Describe the effect of insulin on glucose balance

Answer 9

Decreases plasma levels of:

• Glucose
• Amino acids
• Free fatty acids (FFAs)

Question 10

What are FFAs?

Answer 10

Free fatty acids

Question 11

Describe the mechanisms by which insulin decreases glucose plasma levels:

Answer 11

Insulin increases the rate of uptake of glucose into skeletal muscles and adipose tissue via GLUT4 receptors.

Insulin also drives glucose into the liver.

In both the liver and skeletal muscles, glucose is converted into glycogen. In adipose tissue glucose is converted into triglycerides.

Question 12

What other process does insulin initiate that are not related to glucose?

Answer 12

Insulin increases the uptake of amino acids into muscles and FFAs into adipose tissue.

Question 13

Summarise the structure of insulin:

Answer 13

Comprised of an A, B and C chain. To become biologically active the C chain is cleaved.

Question 14

Where insulin degraded? What enzyme is responsible for insulin degradation? Why is it essential that this enzyme functions properly?

Answer 14

Insulin is degraded in the liver by insulinase/IDE.

If insulinase isn’t functioning properly, insulin can build up in systemic circulation and reach toxic levels. This could cause blood glucose levels to fall dangerously low.

Question 15

Describe the process via which insulin secretion occurs:

Answer 15

1. Glucose enters the cell and is phosphorylated, then respired, releasing ATP.
2. This causes the ATP to ADP ratio to go up. This causes ATP sensitive K+ channels to shut
3. K+ ions remain in the cell and eventually build up, causing the cell to depolarise
4. Depolarisation triggers VG Ca2+ channels to open, Ca2+ rushes in.
5. Ca2+ binds to insulin vesicles triggering secretion

Question 16

What part of the insulin secretion mechanism can be used as a drug target? Why does this work?

Answer 16

The ATP sensitive K+ channel can be used as a drug target.

This works because when certain chemicals bind to the channel, they cause it to shut. In doing so this causes the K+ concentration inside the cell to rise as it typically should.

Question 17

Describe the overall changes in plasma insulin levels during the absorptive and post absorptive states:

Answer 17

Absorptive state - Plasma insulin increases

Post absorptive state - Plasma insulin decreases

Question 18

Describe the mechanism of action for insulin reception

Answer 18

Acts via dimerisation.

1. Insulin binds to external alpha subunits of the receptor
2. Causes tyrosine residues from the beta subunits to become phosphorylated
3. They in turn effect kinases/phosphatases
4. Which in turn effect key enzymes that induce a cellular response

Question 19

What actions does insulin have on carbohydrate metabolism?

Answer 19

Facilitates glucose entry into skeletal muscles.

Stimulates the liver to store glucose as glycogen.

Thereby decreasing concentration of glucose in the blood.

Question 20

What actions does insulin have on lipid metabolism?

Answer 20

Promotes synthesis of fatty acids in the liver, increasing lipoproteins in circulation, increasing release of FAs.

Inhibits breakdown of fat in adipose.

Promotes glycerol synthesis from glucose and increases triglyceride synthesis.

Question 21

Summarise how insulin stimulates glucose uptake:

Answer 21

Insulin binds to Insulin RTKs on the cell-surface membrane.

This causes glucose transporters to be released from storage microsomes and inserted into the membrane.

Additionally, the binding of insulin causes glucose transporter expression to increase.

Question 22

How can insulin sensitising drugs stimulate glucose uptake?

Answer 22

They can bind to insulin receptors on the cell-surface membrane and trigger the release of glucose transporters from storage microsomes.

Question 24

Describe the effect of insulin on skeletal muscle tissue:

Answer 24

Insulin binds to receptors in the muscle tissue, stimulating glucose and amino acid uptake.

Once inside the cells, insulin also promotes the formation of glycogen and structural proteins.

Question 25

Summarise the glucose pathway in skeletal muscles:

Answer 25

Glucose is absorbed via GLUT4 transporters, after which it is phosphorylated in order to remain inside the cell and to make it more chemically active. Glucose-6-P is then either converted into glycogen as an energy store, or broken down into lactic acid and sent to the liver, thereby releasing energy.

Question 26

Describe the effect of insulin on the liver (in terms of enzymes):

Answer 26

Insulin binds to cell surface receptors in the liver, affecting a variety of enzymes: - Stimulates glycogen synthetase, increasing glycogen synthesis - Stimulates glucokinase, increasing glucose phosphorylation - Inhibits glucose-6-phosphatase, decreasing glucose dephosphorylation

Question 27

Summarise the glucose pathway in the liver:

Answer 27

Glucose is absorbed by glucose transporters into the liver cell where it is then phosphorylated. Glucose-6-P is then converted into glycogen as an energy store or pyruvate via glycolysis. If converted into pyruvate it will then undergo decarboxylation into FAs in order to form lipoproteins. These lipoproteins are then sent to adipose tissue.

Question 28

How do insulin sensitising drugs that target the liver influence glucose levels?

Answer 28

They reduce rates of gluconeogenesis thereby decreasing secretions of glucose from the liver into the bloodstream.

Question 29

Describe the effect of insulin on adipose tissue:

Answer 29

Insulin binds to insulin RTKs on the cell-surface membrane, stimulating the uptake of glucose via GLUT4 transporters. Insulin also stimulates lipoprotein lipase, encouraging the breakdown of lipoproteins into fatty acids.

Question 30

Summarise the glucose pathway in adipose tissue:

Answer 30

Glucose is absorbed via GLUT4 transporters into the adipose tissue where it is then phosphorylated or converted into glycerol phosphate. Glucose-6-P then undergoes a series of reactions to form fatty acids. Glycerol phosphate then reacts with the FAs in order to form triglycerides.

Question 31

What are lipoproteins? What is their purpose?

Answer 31

Lipoproteins are molecules made of of polypeptide chains and lipids such as FAs and triglycerides. They serve as a form of lipid transport in water-based environments such as systemic circulation, in which lipids cannot be transported on their own.

Question 32

Summarise the amino acid pathway in adipose tissue:

Answer 32

Amino acids are absorbed into the adipose tissue by co-transport with Na+. Once absorbed, they undergo a series of reactions in order to form FAs which bind with glycerol phosphate in order to form triglycerides.

Question 33

Summarise the lipoprotein pathway in adipose tissue:

Answer 33

Lipoproteins are absorbed into adipose tissue via endocytosis

Question 34

Summarise the effects of insulin secretion on the body:

Answer 34

- Increased rate of glucose uptake - Increased glucose utilisation and ATP generation - Increased glycogenesis - Increased protein synthesis - Increased fat synthesis

Question 35

Define glucose utilisation:

Answer 35

A term describing processes in which glucose is metabolised

Question 36

What cells secrete glucagon?

Answer 36

Alpha-cells of Islets of Langerhans

Question 37

What cells secrete insulin?

Answer 37

Beta-cells of Islets of Langerhans

Question 38

What cells secrete somatostatin?

Answer 38

Delta-cells of Islets of Langerhans

Question 39

What is meant by insulin and glucagon being counter-regulatory?

Answer 39

They have opposite regulatory effects. Insulin acts to decrease blood glucose whereas glucagon acts to increase blood glucose.

Question 40

Summarise the effects of glucagon secretion on the body and where the effects occur:

Answer 40

- Increased glycogenolysis (liver and skeletal muscle) - Increased fats to FAs - Increased protein breakdown - Increased gluconeogenesis (liver)

Question 41

What state drives glucagon secretion?

Answer 41

The post-absorptive/post-fed state

Question 42

What state drives insulin secretion?

Answer 42

The absorptive/fed state

Question 43

What can occur if glucagon levels remain high for a long period of time?

Answer 43

High rates of protein and fat breakdown can lead to loss of skeletal muscle and adipose tissue, resulting in weight loss. Additionally, blood glucose levels can rise too high, depending on the reasons for glucagon levels being high (not enough food intake or are secretion levels unnecessarily high?)

Question 44

Define hypoglycaemia and state the associated blood glucose range:

Answer 44

When blood glucose levels are lower than typical. Blood glucose <3mM.

Question 45

Define hyperglycaemia and state the associated blood glucose range:

Answer 45

When blood glucose levels are higher than typical. Blood glucose >7-10mM (depending on whether fasted or fed).

Question 46

What can cause hypoglycaemia in patients with type I diabetes?

Answer 46

Poorly managed or miscalculated insulin administration can lead to too much glucose being pulled out of the blood.

Question 47

Define type I diabetes:

Answer 47

Sustained high basal blood sugar levels due to the immune system attack beta-cells of the pancreas.

Question 48

Define type II diabetes:

Answer 48

Sustained high basal blood sugar levels due to the body producing insufficient insulin, or being highly resistant to insulin.

Question 49

What is the difference between type I and type II diabetes?

Answer 49

Type I diabetes is an autoimmune disease whereas type II diabetes is characterised by insulin resistance.

Question 50

Define gestational diabetes:

Answer 50

Sustained high basal blood sugar levels during or associated with pregnancy.