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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

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
disadvantages of islet transplants
- 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
26
How amy islet transplant protocols be improved?
Whole pancreas transplantation alternative sites of injection improved culture of islets before ejection
27
advantages of islet transplant
- minor procedure - reduced hypoglycaemic events - reduces requirement of insulin injections - less expensive than artificial pancras
28
Generation of B-cells using embryonic stem cells
- 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
what are the challenges of using ES to treat diabetes
- 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
benefits of using ES to treat diabetes
- unlimited supply
31
induced pluripotent stem cells (iPS)
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
iPS cells are turned into B cells
in vitro and then transplanted into the body acting as functioning beta-cells
33
how are iPS cells different from stem cells
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
iPS cell-based generation of insulin producing cells
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
medical application of IPS cell-based generation of insulin producing cells
- personalised treatment - replacement therapies - correction of genetic defects - circumvention of requirement of immunosuppressants
36
benefit of Stem cells and iPS over islet transplant
no need for immunosuppresents
37
challenges of tips cell-based generation of insulin producing cells
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
what is a theracyte
a device which encapsulates pancreatic islets, shown tp protect against allograft rejection --> however its capacity to do this has not been studied thoroughly
39
what size is a theracyte
4-20uL
40
structure of theracyte
- oblong shape - loading port t one end - outer membrane is vascularising - inner cell has an impermeable membrane
41
theracytes allow
allows flow of oxygen and nutrients into it, but not immune cells which cause rejection
42
transdifferentiation and regeneration of B-cells.
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
introduction of which genes into liver cells might be sufficient to transform them directly into B-cells
PAX4
44
outline transdifferentiation process in a wild type Rag1+ mouse
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
long term administration of what can induce alpha cell mediate beta-like cell neogenesis
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
GABA administration to mediate regeneration of existing B-cells by causing
alpha cell mediated B like cell neogenesis through the down regulation of Ax expression alpha cells (formulation of B-like cells
47
benefits of regenerating B-cells
- no transplants - no glucose monitoring - no insulin injections
48
limitations of regeneration B cell
requires long exposure to GABA- unknown side effects
49
What evidence is there to suggest that beta-cell regeneration might be possible in patients with type 1 diabetes?
increased proliferation of islet cells in patients with recent onset diabetes
50
what enhances murine beta-cell proliferation in mice
NECA
51
evidence behind fasting-mimicking diets
a periodic short-term diet that mimics fastening modulates B-cell regeneration and promotes insulin secretions dn glucose homeostasis (T1DM and T2DM)
52
how does regular insulin ensure slow absorption
forms hexers around lions ions
53
how do rapid acting analogues speed up insulin delivery
changes in aa sequence disrupt dimer formation- meaning faster absorption and rapid onset of action
54
how does detemir ensure long-acting effec
myristic acid bound to lysin B29- promotes self associating and binding to albumin
55
alternative to insulin injection
inhaled insulin
56
name an insulin which can be enhaled
Exubera
57
Exubera
Exubera, developed by Pfizer, is an inhaled powder insulin product
58
development of an insulin molecule which can be inhaled involec
stabilisation of the insulin molecule to make it bioavailable in the dry powder form
59
Exubera was on the marker
for less than a year
60
inhaled insulin is administerd
befor emeals
61
how is inhaled insulin formulated
with a novel carrier that dissolves instantly in long fluid, causing absorption of insulin to be very rapid
62
inhaled insulin dissapears
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
SMART insulin
developed to minimise the number of administrations 'smart insulin would circulate in the body, inactive, until blood glucose levels started to rise'
64
mircroneedle-array patches
- patches have many tiny 'micro-needles' on one survive to project into the ski.
65
what do micro needs contain
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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