L16- Gene to organism

Question 1

What is Type 1 Diabetes Mellitus?

Answer 1

• Insulin dependent

* Loss of pancreatic beta cells

Question 2

What is Type 2 Diabetes Mellitus?

Answer 2

• Insulin independent

* Compromised insulin signalling

Question 3

How are type 1/2 diabetes treated?

Answer 3

• Type 1- insulin

* Type 2- Agents that increase insulin release (Katp blockers or insulin sensitisors)

Question 4

What are diabetic complications?

Answer 4

• Vasculopathy (loss of microcirculation)
• Retinopathy (loss of sight)
• Neuropathy (loss of sensation, pain chronic, loss of autonomic function)

Question 5

How does hyperglycaemia occur?

Answer 5

• Liver/adipose tissue use insulin dependent glucose transporters (GLUT4)
• Lack of insulin means less insulin signalling so glucose remains in plasma due to reduced uptake by cells

Question 6

How is glucose normally stored?

Answer 6

• Insulin dependent uptake
• Glucose converted to glucose-6-phosphate to allow transport
• Glucose stored as fat or glycogen

Question 7

Is increased glucose uptake a problem?

Answer 7

• Increased glycolysis leads to increased formation of reactive and potentially harmful metabolites

Question 8

What is the polyol pathway?

Answer 8

Aldose reductase converting glucose to fructose

Question 9

What happens in oxidative stress from increased glycolysis?

Answer 9

• Reactive metabolites promote oxidation of KEAP1
• KEAP1 keeps Nrf2 inactive
• KEAP1 oxidation releases Nrf2 into nucleus
• Induces expression of antioxidant response element enzymes

Question 10

What is TRPA1?

Answer 10

• Ion channel causing responses to pain, cough and increasing local blood flow
• Target for ROS and electrophiles

Question 11

What happens to Nrf2 in diabetes?

Answer 11

• Persistent oxidative stress results in loss of Nrf2 signalling
• Nrf2 is short lived as it is constantly degraded
• May promote cancer cell survival and cause renal damage