watson - diabetes Flashcards

1
Q

diabetes leads to wasting of tissue and excessive urine production T/F

A

T

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

how is insulin produced

A

by the pancreatic beta cells

synthesised as preproinsulin and is then cleaved

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is the difference between the onset of type 1 and type 2 diabetes

A

type 1 diabetes is typically adolescent onset whereas type 2 is mature onset

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is different about the insulin requirement of type 1 and type 2 diabetes

A

type 1 has an absolute requirement for insulin whereas type 2 may not require insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is different about the outcome of type 1 and 2

A

type 1 can be fatal without treatment - regular injections of insulin. type 2 can be modified by exercise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are the key tissues that control glucose homeostasis

A

pancreas
muscle
liver
adipose tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what molecule do pancreatic alpha cells produce

A

glucagon - has opposite effects to insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

pancreatic beta cells produce insulin and this acts in an endocrine manner. what does this mean

A

the insulin hormone is released and diffused through tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what molecules are important in determining when pancreatic beta cells produce insulin

A

kir 6.2 - ATP gated inward rectifying K+ channel
L-type Ca channel
GLUT-2 - glucose transporter
hexokinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

glucose enters the cell via what

A

GLUT2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

when glucose enters the cell it is phosphorylated by what to prevent it leaving the cell

A

hexokinase IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

after phosphorylation G-6-P is metabolised by mitochondria which alters levels of what to act as a sensor for circulating glucose levels

A

ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

As the ATP levels in the cell increase the KIR6.2 potasssium channel shuts what does this cause

A

a negative potential and the calcium channel to open and calcium influx into cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what does the influx of calcium into the cell cause

A

catalyses the membrane fusion of secretory granules and release of insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

the specific receptor for insulin is in which family

A

receptor tyrosine kinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

when insulin binds to receptor the phosphorylation of the receptor leads to the activation of serine/threonine kinases which leads to phosphorylation of a series of what

A

insulin-receptor subtrates (IRS-1 to IRS-4)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

which pathway does the phosphorylation of IRS-1/IRs-2 activate

A

phosphoinositol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what does activation of the phosphoinositol pathway lead to

A

activation of Akt which is the main mediator od metabolic actions of insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what does Akt signalling drive

A

cytoskeleton rearrangements that lead to insertion/activation of GLUT4 - increases uptake of glucose 20 fold

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what does the uptake of glucose but GLUT-4 stimulated by insul-Aktcause

A

reduces blood glucose levels

21
Q

what is the effect of insulin/akt in the liver

A

decreases gluconeogenesis
increase glycogenesis
downregulates glycogenolysis
increases lipogenesis

22
Q

what is the effect of insulin/akt in the muscles

A

glucose transport increases via GLUT4

stimulates glycogenesis

23
Q

what is the effect of insulin/akt in adipocytes

A
  • Increase in glucose transport via GLUT4
  • Increase in lipogenesis
  • Decrease in lipolysis (breakdown of fats)
24
Q

what are the 2 main stages of the evolution of type 2 diabetes

A

loss of insulin sensitivity

loss of insulin production by pancreatic b cells

25
Q

describe the stages of the evolution of type 2 diabetes

A

go through a period where glucose levels in blood rise
B cells sense this and produce more insulin to drive it down to normal levels
cells no longer respond to insulin
glucose levels steadily increase
B cells cant keep producing insulin at this high output - go into decline
blood glucose continurs to rise and gets out of control as insulin production falls

26
Q

in type 2, diagnosis occurs after insulin production has fallen sufficiently that blood glucose levels rise to symptoms of hyperglycaemia T/F

A

T

27
Q

type 2 causes an increase in fatty acids in circulation, why

A

lipolysis is not inhibited by insulin

28
Q

what are the effects of hyperglycaemia which are common to both type 1 and type 2

A
polyuria
neuropathy
macrovascuar damage
microvascular damage
infection increased
29
Q

what is the functional unit of the kidney

A

nephron

30
Q

how does diabetes lad to polyuria

A

filtrate contains glucose and now has osmotic pressure - cant transport all water back out of filtrate

31
Q

how does diabetes lead to microvascular complications

A

high glucose concs are toxic to endothelial cells lining the capillaries
induce expression of fibrogenic growth factor
increased deposition of matrix in basement membrane
thickening of vessel wall
loss of circulation

32
Q

how does diabetes lead to macrovascular complications

A

prolonged high levels of glucose increases permeability of endothelial cells lining the arteries
can lead to deposits of lipids in supportive layer of vessels - atheroma

33
Q

how does diabetes lead to neuropathy

A

prgressive loss of nerve function associated with prolonged exposure to glucose

34
Q

how does diabetes lead to infection

A

high levels of tissue glucose provides good habitat for microorgansims
• Reduced microvascular function changes the nature of normal inflammatory response
• Reduced diffusion of inflammatory mediators
• Reduced migration of immune cells
• Peripheral neuropathy can reduce awareness of damage

35
Q

T2D has a stronger genetic basis than T1D BUT

A

depends on the environment

36
Q

what are the genes involved with T2D

A

calpain10
glucokinase
GLUT2

37
Q

what are sulfonureas

A

intervention for T2D

38
Q

how do sulfonureas work

A

target SUR1 subunit of ATP gated potassium channel blocks it

triggers Ca influx and increased insulin secretion

39
Q

how does metaformin work as an intervention for T2D

A

increases insulin receptor signalling sensitivity

40
Q

what is the differences between T1 and T2

A

T2 doesnt require insulin in early stages T1 does
Type 2 has a mature onset T1 has adolescent
T2 can be managed by diet T1 cant
Type 1 is an autoimmune disease

41
Q

A number of high affinity autoantibodies against beta cell proteins are detected in patientswith T1D

A

T

42
Q

what are the autoantibodies in T1D patients usually against

A
  • Glutamic acid decarboxylase
  • Insulin
  • Zinc transporter 8
  • Insulin associated antigen 2
43
Q

HLA alleles account fr around % of Type 1 risk

A

40-50%

44
Q

how were the risk alleles of T1D identified

A

Using NOD mouse

45
Q

what is Idd-2 and how is it associated with T1D

A

polymorphism in region upstream from insulin

causes decreased levels of expression of insulin in thymus - T cells that react to it are not all destroyed

46
Q

how is IL-2 associated with T1D

A

necessary for generation of Tregs

if theres not enough Tregs this leads to autoimmunity

47
Q

how is idd-4 associated with T1D

A

locus associated with aberrant overexpression of IFN response to viral infection in the NOD mouse

48
Q

how is CTLA-4 associated with T1D

A

acts to dampen down TCR response

if defective may lead to aberrant response

49
Q

how is PTPN22 associated with T1D

A

reverses the action of tyrosine kinases

important in shutting down tyrosine kinase pathways