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cell proliferation > formation and degradation of pancreatic beta cells > Flashcards

formation and degradation of pancreatic beta cells Flashcards

1
Q

what are islets

A

clusters of ~1000 endocrine cells

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2
Q

how many islets are in a human pancreas

A

~1 million

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3
Q

how much of the pancreatic volume do islets make up

A

~1-2%

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4
Q

what are the islet of langerhans endocrine cell types

A

a, b, delta, epsilon and F

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5
Q

what do alpha-cells secrete

A

glucagon

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6
Q

what do beta-cells secrete

A

insulin

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7
Q

what do delta-cells secrete

A

somatostatin

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8
Q

what do F cells secrete

A

pancreatic polypeptide (PP)

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9
Q

what is neogenesis

A

the formation of new beta cells

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10
Q

what is the master regulator of pancreatic development

A

pancreatic and duodenal homeobox 1 (PDX1)

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11
Q

what drives the beta cell neogenesis (the birth of beta cells)

A

transcription factor Neurogenin3 (Neurog3)

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12
Q

what is beta cell neogenesis

A

formation of new beta cells from ductal progenitors during development

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13
Q

explain the concept of transdifferentiation with reference to extreme beta cell loss

A

lineage tracing has shown alpha and delta cells can transdifferentiate into insulin expressing cells (beta) in mice

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14
Q

what does genetic labelling of alpha cell lineages in the presence of beta cell ablation show

A

that alpha cells can switch on insulin production

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15
Q

how do beta cells proliferate

A

slowly

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16
Q

how can proliferation be measured

A

incorporation of bromodeoxyuridine (BrdU), a thymidine analogue, into newly synthesised DNA during replication: daughter cells are labelled
presence of the Ki67 protein (typically by immunofluorescence): cells in active cell cycle are labelled

17
Q

what is the rate of proliferation in beta cells

A

<0.5%

18
Q

what does harmine do

A

can increase proliferation rates

19
Q

what are the drivers of beta cell proliferation in both rodents and humans

A

glucagon-like peptide 1 (GLP1), insulin signalling and Dyrka1a inhibition

20
Q

what do enteroendocrine L-cells release in response to food uptake

A

GLP-1

21
Q

GLP initiates GCPR signalling in the beta cell to promote what

A

proliferation via a cAMP and PKA dependant mechanism

22
Q

what is beta cell differentiation maintained by

A

transcription factors, such as PDX1, Nkx6.1, PAX6 and MAFA

23
Q

what are the major diabetes complications

A

strokes, cerebrovascular disease, dementia, depression, retinopathy, oral health, coronary heart disease, diabetic kidney disease, sexual dysfunction, complications during pregnancy, neuropathy, peripheral vascular disease, diabetic foot

24
Q

what is the annual cost of managing diabetes in the UK

A

over £10 billion (~10% of the total NHS budget)

25
Q

define beta cell failure in type 2 diabetes

A

insulin resistance + beta cell dysfunction = relative insulin deficiency

26
Q

what are the causes of beta cell apoptosis

A

ER stress, alteration of protein degradation pathways, mitochondrial alteration and oxidative stress and inflammation

27
Q

what happens to beta cells within T2D

A

they degranulate but persist

28
Q

what was the results of an IHC of pancreatic sections using anti-insulin an anti-chromagranin antibody

A

pancreatic insulin+ area and mature insulin granules were reduced in T2D
however, chromagrnin A (endocrine cell marker) was unaltered
suggests degranulation or dedifferentiation of beta cells during T2D

29
Q

what are the therapeutic strategies of T1D

A

protect beta cells from destruction in stages 1 and 2 or replace / regenerate beta cells in stage 3

30
Q

what is T1D

A

an autoimmune disease involving compelx interplay between the beta cell and immune cells, resulting in beta cell destruction

31
Q

what is profiund by the stage of hyperglycaemia and diagnosis in T1D

A

beta cell loss

32
Q

how are beta cells losr in T1D

A

via apoptosis and necrosis

33
Q

how could regeneration of beta cells occur

A

it could theoretically be achieved by neogenesis, replication, re-differentiation (T2D) or transdifferentiation pathways

cell proliferation (12 decks)

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