Lec 16 - Normal insulin release and type 1 diabetes

Question 1

how is release of insulin from the secretory granules triggered

Answer 1

glucose taken up
leading to specific K+ channels closing
memb depol
causes Ca2+ inlfux
calcium induced insulin release

Question 2

what is the mechanism by which insluin released

Answer 2

calcium dependant exocytosis

Question 3

how is it that insulin can be released so quickly when glucose is given

Answer 3

preformed granules
(regulated exocytosis)

Question 4

2 phases of insluin release

Answer 4

1st = transient response= very rapid, peaks quick
2nd = sustained response = prolonged

Question 5

why is 2nd wave slower

Answer 5

need time for gene transcription and insluin biogenesis
formed, packaged, positioned near membrane

Question 6

what is the conc of insluin release dependant on

Answer 6

the conc of glucose

Question 7

T2D: what happens to release of insulin

Answer 7

blunted at all insulin concs
both at initial and sustained

Question 8

what governs the 1st and 2nd phase of insulin release and what does this mean for T2D

Answer 8

beta cells
so it means these cells are defected

Question 9

what does insluin secretagogue therapy do

Answer 9

• promote insluin release
• partial restoration of 1st phase
• 2nd phase also improved

Question 10

how does secretagogue therapy inc insluin release

Answer 10

increases calcium conc in cell

Question 11

what do incretins do

Answer 11

prime pancreas and faciliates enhanced response to glucose loading

Question 12

where are incretins released from

Answer 12

entero endocrine cells of GI tract

Question 13

what are incretins deactivaed by

Answer 13

DPP-4
shortens the half life of GLP-1

Question 14

how come effect of DPP-4 can come on wuickly

Answer 14

released from cells also in the endothelial cells
in gut

Question 15

general definition of diabetes mellitus

Answer 15

a chronic disease which occurs when the islets of langerhans do not produce enough insluin OR when the body cannot effectively use the insluin it produces - leading to hyperglycaemis

Question 16

what 2 main functions does insluin have

Answer 16

• stim pathways for glucose utilisation, storage and uptake
• inhibit pathways for glucose production, glucogenesis, lipolysis

so obvs the opposite of all this happens when insulin low

Question 17

short term effects of hyperglycaemia

Answer 17

• glucosuria = dehydration
• polydipsia = excessive thirst
• diabetic ketoacidosis

Question 18

long term effects of hyper glycaemia

Answer 18

• implications for morbidity and mortality
• key tissues become sensitive to glucose toxicity

Question 19

what cells can glucotoxicity take an effect on

Answer 19

• capillary endothelial cells
• mesangial cells
• neurons
• schwann cells of the periphery

Question 20

what can the glucose toxicity in these cells lead to

Answer 20

• glaucoma, cataracts
• microvascular damage to kidneys, CNS and blood vessels in heart

Question 21

what happens to beta cell mass initially after birth

Answer 21

increases
in healthy idnividuals itll stay at a constant level

Question 22

T1D: what happens to beta cell mass

Answer 22

declines over time irreversibly

Question 23

2 main reasons for beta cell mass decline

Answer 23

• genetic predisposition
• then exposure to a (probably viral) pathogen

Question 24

T1D: what happens when someone exposed to the external pathogen

Answer 24

autoimmune event
body produces antibodies against beta cells= destruction

Question 25

what biomarker for insluin can no longer be detected after clinical onset of T1D

Answer 25

C peptide

Question 26

over the course of T1D treatment, how has insluin origin chanegd

Answer 26

animal insluin -> human insulin -> synthetic insulin analogues

Question 27

T1D: why is islet transplantation as a treatment difficult

Answer 27

high number of islets needed to replace them
not used commonly

Question 28

what does a bionic pancreas do

Answer 28

• algorithm based delivery = automatic release of both insluin and glucagon
• subcutaneous implantation of a monitor to see glucose levels
• also a subcutanous needle impanted to deliver the hormonesw