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(1-5) Translational Medical Science > Trigger 1: T1DM modes of insulin delivery > Flashcards

Trigger 1: T1DM modes of insulin delivery Flashcards

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1
Q

Forms of invasive monitoring of blood glucose

A
  • finger prick test
  • continuous glucose monitoring system (electrode under skin)
  • HbA1c
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2
Q

continuous glucose monitoring system

A

electrode under the skin which measures glucose in tissue fluid

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3
Q

Non-invasive monitoring of blood glucose

A

GlucoseWise sensor (pic)

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4
Q

How do glucowise sensors work

A
  • transmit low power radio waves through sections of the body e.g. fingers, earlobe.
    • ->Which are thin enough for radio waves to pass

-signal is received on opposite side of GlucoWise where data about blood is collected

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5
Q

Insulin analogues

A

laboratory grown but genetically altered to create either a more rapid acting or more uniformly acting form of the insulin. This can have advantages for blood sugar management

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6
Q

Insulin analogues have been proposed to

A

more closely mimic normal human physiology

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7
Q

name two insulin analogues

A

Novorapid and Detemir

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8
Q

Which insulin analogues have a rapid response to blood glucose

A

Novorapid and Aspart

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9
Q

Mode of action of novorapid

A

disrupts dimer formation

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10
Q

Which insulin analogue has a long acting affect on blood glucose

A

Deter and glargine

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11
Q

Mode of action of detemir

A

Promotes self-association and binding to albumin

o Structure: Myristic acid bound to lysine B29

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12
Q

What is an artificial pancreas

A

an automatic treatment for T1Dm

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13
Q

how does the artificial pancreas work?

A

mimics the glucose regulating function of a healthy pancreas by providing a closed loop system which monitors blood glucose level at the same time of adjusting it by release insulin analogues–> close loop system

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14
Q

what do artificial pancreas use to monitor glucose

A

continous glucose monitor- which transmits information an an insulin pump which calculates and releases the required insulin

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15
Q

CGM

A

a sensor is for under the skin, which transfers information to the glucose monitor outside the body

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16
Q

insulin pump in the artificial pancreas is worn..

A

underneath clothes

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17
Q

advantages of artificial pancreas

A
  • reduces time spent in high and low BGL
  • safe and effective
  • rapid
  • sensitive
  • preventative
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18
Q

disadvantages of artificial pancreas

A
  • not cost effective ($5,000-$8,000)
  • CGM measures glucose level i tissue fluid (doesn’t change as quickly as blood )
  • involves patients carrying an additional device
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19
Q

Examples of B cell replacement therapies

A

Islet transplants

Creating of new B-cells

Regeneration of existing B-cells

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20
Q

Methods of creating new B-cells (3)

A

(1) embryonic stem cells
(2) iPs
(3) Transdifferentiation

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21
Q

islet translans

A

pancreatic islets taken from deceased organ donor using specialised enzymes. islets are purified, processed and transplanted into patient

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22
Q

how many donors are required for an islet transplant

A

2

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23
Q

how are islet transplants carried out

A

under local anaesthetic, x rays and ultrasounds, which guide placement of catheter into the portal vein of the LIVER.

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24
Q

where do islet transplant cells make and release insulin

A

the liver

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25
Q

disadvantages of islet transplants

A
  • High levels of cell death occur
  • infections
  • immune suppressing medicines need to be taken to prevent isles form being rejected
  • most individuals still need to take exogenous insulin (not a cure)
  • insulin independence amy not last long term
  • requires several donors = hard to find match
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26
Q

How amy islet transplant protocols be improved?

A

Whole pancreas transplantation

alternative sites of injection

improved culture of islets before ejection

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27
Q

advantages of islet transplant

A
  • minor procedure
  • reduced hypoglycaemic events
  • reduces requirement of insulin injections
  • less expensive than artificial pancras
28
Q

Generation of B-cells using embryonic stem cells

A
  • fertilise egg with sperm
  • embryo develop for a week
  • embryo becomes a blastocyst
  • inner mass of blastocyst is removed and grown in dish
  • culture conditions are changed to stimulate cell to differentiate into B cells
29
Q

what are the challenges of using ES to treat diabetes

A
  • difficult to generate fully functional insulin-producing cells comparable with mature beta cells in vivo.
  • the heterogeneity of the ES progeny is unacceptable in clinical settings
  • May fail to express appropriate beta-cell markers e.g. PDX-1 or co-express other hormones – e.g glucagon
  • risk of teratoma development
  • ethical controversy
  • no long term studies
30
Q

benefits of using ES to treat diabetes

A
  • unlimited supply
31
Q

induced pluripotent stem cells (iPS)

A

are a type of pluripotent stem cell that can be generated directly from adult cells such fibroblasts and act like embryonic stem cells forming any cell type

32
Q

iPS cells are turned into B cells

A

in vitro and then transplanted into the body acting as functioning beta-cells

33
Q

how are iPS cells different from stem cells

A

very similar

however…Embryonic stem cells can become all cell types of the body because they are pluripotent. Adult stem cells are thought to be limited to differentiating into different cell types of their tissue of origin

34
Q

iPS cell-based generation of insulin producing cells

A

1) isolate cells from patient (skin or fibroblasts) and grow in dish
2) treat with reprogramming factors (Oct4, Sox2, Klf4 and c-Myc
3) wait a few weeks
4) pluripotent stem cells
5) change culture conditions to stimulate cells to differentiate into B cells

35
Q

medical application of IPS cell-based generation of insulin producing cells

A
  • personalised treatment
  • replacement therapies
  • correction of genetic defects
  • circumvention of requirement of immunosuppressants
36
Q

benefit of Stem cells and iPS over islet transplant

A

no need for immunosuppresents

37
Q

challenges of tips cell-based generation of insulin producing cells

A

Creating clinically relevant numbers of mature beta-cells

Time/cost – only available for patients not responding to current treatments?

Use of viruses causing random intergration of pluripotency factors resulting in potential mutagenesis

Potential presence of pluripotent cells – teratoma formation

38
Q

what is a theracyte

A

a device which encapsulates pancreatic islets, shown tp protect against allograft rejection –> however its capacity to do this has not been studied thoroughly

39
Q

what size is a theracyte

A

4-20uL

40
Q

structure of theracyte

A
  • oblong shape
  • loading port t one end
  • outer membrane is vascularising
  • inner cell has an impermeable membrane
41
Q

theracytes allow

A

allows flow of oxygen and nutrients into it, but not immune cells which cause rejection

42
Q

transdifferentiation and regeneration of B-cells.

A

is a process in which one mature somatic cell transforms into another mature somatic cell without undergoing an intermediate pluripotent state or progenitor cell type

43
Q

introduction of which genes into liver cells might be sufficient to transform them directly into B-cells

A

PAX4

44
Q

outline transdifferentiation process in a wild type Rag1+ mouse

A

1) adenovirus used to deliver Ngn3, Pdx-1 and Mafa (TFs) to pancreas
2) Wild type pancreas is predominantly exocrine tissue with insulin beta-cells in the islet
3) one months after infection infection with TF, numerous insulin cells appear outside of islet

45
Q

long term administration of what can induce alpha cell mediate beta-like cell neogenesis

A

GABA

  • B-cells generated are functional and can replace endogenous B cells
  • GAB appears to also convert human and rat alpha cells into B-like cells
46
Q

GABA administration to mediate regeneration of existing B-cells by causing

A

alpha cell mediated B like cell neogenesis through the down regulation of Ax expression alpha cells (formulation of B-like cells

47
Q

benefits of regenerating B-cells

A
  • no transplants
  • no glucose monitoring
  • no insulin injections
48
Q

limitations of regeneration B cell

A

requires long exposure to GABA- unknown side effects

49
Q

What evidence is there to suggest that beta-cell regeneration might be possible in patients with type 1 diabetes?

A

increased proliferation of islet cells in patients with recent onset diabetes

50
Q

what enhances murine beta-cell proliferation in mice

A

NECA

51
Q

evidence behind fasting-mimicking diets

A

a periodic short-term diet that mimics fastening modulates B-cell regeneration and promotes insulin secretions dn glucose homeostasis (T1DM and T2DM)

52
Q

how does regular insulin ensure slow absorption

A

forms hexers around lions ions

53
Q

how do rapid acting analogues speed up insulin delivery

A

changes in aa sequence disrupt dimer formation- meaning faster absorption and rapid onset of action

54
Q

how does detemir ensure long-acting effec

A

myristic acid bound to lysin B29- promotes self associating and binding to albumin

55
Q

alternative to insulin injection

A

inhaled insulin

56
Q

name an insulin which can be enhaled

A

Exubera

57
Q

Exubera

A

Exubera, developed by Pfizer, is an inhaled powder insulin product

58
Q

development of an insulin molecule which can be inhaled involec

A

stabilisation of the insulin molecule to make it bioavailable in the dry powder form

59
Q

Exubera was on the marker

A

for less than a year

60
Q

inhaled insulin is administerd

A

befor emeals

61
Q

how is inhaled insulin formulated

A

with a novel carrier that dissolves instantly in long fluid, causing absorption of insulin to be very rapid

62
Q

inhaled insulin dissapears

A

more quickly than subcutaneously delivered rapid-acting insulin–> causing rapid drop in glucose levels which return to normal in shorter time than subcutaneous injection

63
Q

SMART insulin

A

developed to minimise the number of administrations

‘smart insulin would circulate in the body, inactive, until blood glucose levels started to rise’

64
Q

mircroneedle-array patches

A
  • patches have many tiny ‘micro-needles’ on one survive to project into the ski.
65
Q

what do micro needs contain

A

nanoparticles: insulin, glucose oxidase, polymer that dissembles in hypoxic conditions
 Needles enter skin
 In presence of glucose in extracellular fluid, glycose enters needle  glucose oxidase: glucose  gluconic acid  uses up oxygen = hypoxia  polymer breaks down  insulin released

(1-5) Translational Medical Science (26 decks)

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