TRICKY-learn

Question 1

name two smart insulins

Answer 1

• microneedle array patches

- modified insulin molecule

Question 2

how do micro needle array patches work?

Answer 2

insulin contained in polymer that dissociates in hypoxic conditions
- e.g. when blood glucose levels rise- polymer dissociates and releases insulin

Question 3

when does insulin polymer dissociate

Answer 3

during hypoxic conditions - when glucose levels rise

Question 4

what do smart insulins ahem to be

Answer 4

• rapidly active when blood glucose rise

- inactive when blood glucose low

Question 5

modified insulin molecules have what region

Answer 5

an albumin binding region and glucose sensor

Question 6

modified insulin molecules release insulin when

Answer 6

glucose levels are high

Question 7

albumin

Answer 7

prevents insulin from having its affect on cells

Question 8

example of a slow acting insulin analogue

Answer 8

Detemir and Glargine

Question 9

determine and glargine

Answer 9

associate with albumin and only release insulin when glucose levels fall

Question 10

islet autoantibodiesare produced against

Answer 10

a small number of proteins e.g. insulin and GAD

Question 11

how are autoanitbodie sproduces

Answer 11

proteins are aberrantly processed and presented to the immune system during process of islet autoimmunity (CD4- B cell)

Question 12

islet autoantibodies are not

Answer 12

directly pathogenic

Question 13

islet autoantibodies are regarded as

Answer 13

markers for disease rather than causative agents

Question 14

some people will develop autoantiboides

Answer 14

even thought they don’t have T1D

Question 15

what is added to DNA to measure methylation

Answer 15

sodium bisulphite

Question 16

decribe process of measuring DNA methylation

Answer 16

1) DNA treated with sodium bisulphite
2) sodium bisulphite converts all unmethylated cytosine into uracil
3) Uracil then converted to thymidine during PCR

Question 17

what can sodium bisulphite treated DNA be used for

Answer 17

various types of sequencing

Question 18

outline types of sequencing used in epigenetics

Answer 18

• pyroseqeuncing
• illumine 450k DNA methylation arrays
• bisulphite whole genome sequencing

Question 19

HDAC inhibitors and TBI

Answer 19

HDACi upregulate transcription of neuroprotective genes

Question 20

what does up regulation of neuroprotective genes cause

Answer 20

cell survival, proliferation and differentiation

Question 21

what do HDACi suppress

Answer 21

inflammatory responses

Question 22

HDACi promote

Answer 22

neurogenesis

Question 23

HDACi stimulate

Answer 23

axonal regeneration

white and grey matter

Question 24

name a HDACi

Answer 24

vorinostat

Question 25

glucokinase affinity

Answer 25

(s0.5, 8-10mM)

Question 26

which drugs increase renal excretion of glucose

Answer 26

- GLP-1 agonists | - sulphonylureas

Question 27

B cell replacement therapies (3)

Answer 27

- Islet transplants - Creating new B cell - Regeneration of existing B cells

Question 28

methods of creating new B cells

Answer 28

- ES cells - iPS - transdifferentiation

Question 29

B cell transplant technique

Answer 29

carried out under local anaesthetic, X-ray and ultra sounds used to guide placement of catheter into portal vein of liver

Question 30

generation of B cells using embryonic stem cells

Answer 30

1) fertilise egg with sperm 2) let embryo develop for a week 3) embryo become blastocysts 4) inner mass of blastocyst removed and grown in dish 5) culture conditions changes to stimulate cells to differentiate into B cells

Question 31

iPS

Answer 31

induces pluripotent stem close

Question 32

how does iPS work

Answer 32

type of stem cells generated from adult cells such as skin and fibroblast- its like eStem cell

Question 33

iPS metho

Answer 33

1) isolate cells from patient (skin) and grow ind wish 2) treat with reprogramming factors (Oct4, Sox4, Klf4 and c-myc 3) wait for a few weeks 4) pluripotent stem cells 5) change culture conditions and stimulate to become B cell

Question 34

reprogramming factors

Answer 34

Oct4 Sox4 Klf4 C-myc

Question 35

negative of stem cell production of B cell

Answer 35

- generated B cells may not be comparable to mature B cells - risk of teratoma formation - ethical controversy - no long term studies

Question 36

negatives of induced pluripotent stem cell production of B cells

Answer 36

- creating a clinically relevant number of mature B cells - time and cost - teratoma formation

Question 37

thoraces are

Answer 37

islet encapsulation devices

Question 38

curative B cell transplationation is hampered by

Answer 38

persistence of auto reactive immune cells which require a high dose of immunosuppressants

Question 39

therapy device is a method of

Answer 39

conveying grade protection and preventing need for immunosuppressants

Question 40

theracytes allos

Answer 40

transfer of oxygen and nutrients to islet cells

Question 41

theracytes stop

Answer 41

immune cels from making direct contact with islet graft

Question 42

introduction of which gene into liver cells may be enough to transform into B cell

Answer 42

PAX4

Question 43

which drug has been used to induce alpha cells to become B cells

Answer 43

GAB

Question 44

GABA does what to alpha cells

Answer 44

downregulates Ax expression --> become B cells

Question 45

inhaled insulin

Answer 45

disappears more rapidly than subcutaneous injection- rapidly drops glucose levels

Question 46

how does insulin ensure slow absorption

Answer 46

forms hexamer- unit of insulin molecules-

Question 47

hexamers

Answer 47

inactive

Question 48

rapid insulin analogues (novorapid and apart)

Answer 48

change in aa sequence disrupts dimer formation- faster absorption

Question 49

insulin is only active as a

Answer 49

monomer