l3 metabolic diseases

Question 1

why is diabetes an important target for modelling human disease?

Answer 1

• diabetes is a fast growing health threat
  -becoming more and more common
• UK has 3 million sufferers
  (type 2 majority)

Question 2

what are type 1 and type 2 diabetes ?

Answer 2

type 1 - not enough insulin/B cells being produced
(usually congenital)
type 2 - B cells and insulin produced OK but body is resistant to the effects of of insulin

Question 3

where is insulin produced?

Answer 3

In the Beta cells of the islets of lagerhans in the pancreas

- insulin stimulates peripheral tissues to take up glucose (e.g. skeletal muscle)

Question 4

what happens at late stages of type 2 diabetes?

Answer 4

Overtime B cell levels deplete (as body is not responding to insulin there is no point B cells being produced)
- this exacerbates the condition
- secondary knock on effects
(T1 and T2 both end up with depletion of B cells)

Question 5

what can be caused by persistently high levels of blood glucose?

Answer 5

• can cause damage to bodies tissues
• e.g. cause blood vessel and nerve damage
• eye issues - cataracts - glaucoma
• increased risk of heart attack and stroke
• poor kidney function - kidney failue
• increased risk of obesity and death

Question 6

what occurs after hyperinsulinemia in T2D patients?

Answer 6

• develop insulin resistance
• declining insulin levels (B cell dysfuntion)
• impaired glucose tolerance

Question 7

what are the triggers of T2D?

Answer 7

obesity + 2 other components (e.g. low HDL, high LDL, high BP)

Question 8

what time of obesity if associated with diabetes?

Answer 8

• abdominal adiposity
• high correlation between waist circumferance in women and risk of developing T2D
• excess fat in ectopic sites e.g. accumulate in muscle and liver)

Question 9

what are the 3 major metabolic defects that result in T2D?

Answer 9

• peripheral tissues resistant to taking up insulin
• liver increases glucose production
• pancreas decreasing level of insulin secretion/B cells

Question 10

why is it inclear how obesity results in diabetes?

Answer 10

many tissues interact

Question 11

what happens in mice with lack of adipose tissue?

Answer 11

• hyperphagia (eat too much)
• result in hyperglycemia, insulin reistance and T2D
• due to deficiency of leptin? (produced by apidocytes)

Question 12

what is leptin?

Answer 12

a hormone produced by apidocytes which inhibits hunger

• acts on arcuate nucleus of the hypothalamus to achieve energy homeostasis
• leptins actions are opposed by ghrelin (hunger hormone)

Question 13

what is a liver specific promoter?

Answer 13

pepck

Question 14

what do transgenic reporter lines allow us to analyse?

Answer 14

Analyse tissues in

• healthy animals
• animals with a genetic mutation
• animals exposed to a certain environment

Question 15

what were the transgenics used when identifying the endocrine and exocrine pancreas?

Answer 15

endocrine pancreas - Tg(fabp10,dsred)
exocrine pancreas- Tg(ptf1a, GFP)
B cells of exocrine pancreas - Tg(Ins, Kaede)

Question 16

what do reporter lines depend on?

Answer 16

depend on the fact that different genes are differentially transcribed in different tissues due to intercations betweeen enhancer/promoter regions and different TFs.

Question 17

what are the 2 different types of glucose?

Answer 17

• postprandial glucose - after a meal
• fasting glucose - not after a meal

(both increase over time in T2D cases)