formation and degradation of pancreatic beta cells

Question 1

what are islets

Answer 1

clusters of ~1000 endocrine cells

Question 2

how many islets are in a human pancreas

Answer 2

~1 million

Question 3

how much of the pancreatic volume do islets make up

Answer 3

~1-2%

Question 4

what are the islet of langerhans endocrine cell types

Answer 4

a, b, delta, epsilon and F

Question 5

what do alpha-cells secrete

Answer 5

glucagon

Question 6

what do beta-cells secrete

Answer 6

insulin

Question 7

what do delta-cells secrete

Answer 7

somatostatin

Question 8

what do F cells secrete

Answer 8

pancreatic polypeptide (PP)

Question 9

what is neogenesis

Answer 9

the formation of new beta cells

Question 10

what is the master regulator of pancreatic development

Answer 10

pancreatic and duodenal homeobox 1 (PDX1)

Question 11

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

Answer 11

transcription factor Neurogenin3 (Neurog3)

Question 12

what is beta cell neogenesis

Answer 12

formation of new beta cells from ductal progenitors during development

Question 13

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

Answer 13

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

Question 14

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

Answer 14

that alpha cells can switch on insulin production

Question 15

how do beta cells proliferate

Answer 15

slowly

Question 16

how can proliferation be measured

Answer 16

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

Question 17

what is the rate of proliferation in beta cells

Answer 17

<0.5%

Question 18

what does harmine do

Answer 18

can increase proliferation rates

Question 19

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

Answer 19

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

Question 20

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

Answer 20

GLP-1

Question 21

GLP initiates GCPR signalling in the beta cell to promote what

Answer 21

proliferation via a cAMP and PKA dependant mechanism

Question 22

what is beta cell differentiation maintained by

Answer 22

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

Question 23

what are the major diabetes complications

Answer 23

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

Question 24

what is the annual cost of managing diabetes in the UK

Answer 24

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

Question 25

define beta cell failure in type 2 diabetes

Answer 25

insulin resistance + beta cell dysfunction = relative insulin deficiency

Question 26

what are the causes of beta cell apoptosis

Answer 26

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

Question 27

what happens to beta cells within T2D

Answer 27

they degranulate but persist

Question 28

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

Answer 28

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

Question 29

what are the therapeutic strategies of T1D

Answer 29

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

Question 30

what is T1D

Answer 30

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

Question 31

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

Answer 31

beta cell loss

Question 32

how are beta cells losr in T1D

Answer 32

via apoptosis and necrosis

Question 33

how could regeneration of beta cells occur

Answer 33

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