Lec 16 - Normal insulin release and type 1 diabetes Flashcards
how is release of insulin from the secretory granules triggered
glucose taken up
leading to specific K+ channels closing
memb depol
causes Ca2+ inlfux
calcium induced insulin release
what is the mechanism by which insluin released
calcium dependant exocytosis
how is it that insulin can be released so quickly when glucose is given
preformed granules
(regulated exocytosis)
2 phases of insluin release
1st = transient response= very rapid, peaks quick
2nd = sustained response = prolonged
why is 2nd wave slower
need time for gene transcription and insluin biogenesis
formed, packaged, positioned near membrane
what is the conc of insluin release dependant on
the conc of glucose
T2D: what happens to release of insulin
blunted at all insulin concs
both at initial and sustained
what governs the 1st and 2nd phase of insulin release and what does this mean for T2D
beta cells
so it means these cells are defected
what does insluin secretagogue therapy do
- promote insluin release
- partial restoration of 1st phase
- 2nd phase also improved
how does secretagogue therapy inc insluin release
increases calcium conc in cell
what do incretins do
prime pancreas and faciliates enhanced response to glucose loading
where are incretins released from
entero endocrine cells of GI tract
what are incretins deactivaed by
DPP-4
shortens the half life of GLP-1
how come effect of DPP-4 can come on wuickly
released from cells also in the endothelial cells
in gut
general definition of diabetes mellitus
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
what 2 main functions does insluin have
- 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
short term effects of hyperglycaemia
- glucosuria = dehydration
- polydipsia = excessive thirst
- diabetic ketoacidosis
long term effects of hyper glycaemia
- implications for morbidity and mortality
- key tissues become sensitive to glucose toxicity
what cells can glucotoxicity take an effect on
- capillary endothelial cells
- mesangial cells
- neurons
- schwann cells of the periphery
what can the glucose toxicity in these cells lead to
- glaucoma, cataracts
- microvascular damage to kidneys, CNS and blood vessels in heart
what happens to beta cell mass initially after birth
increases
in healthy idnividuals itll stay at a constant level
T1D: what happens to beta cell mass
declines over time irreversibly
2 main reasons for beta cell mass decline
- genetic predisposition
- then exposure to a (probably viral) pathogen
T1D: what happens when someone exposed to the external pathogen
autoimmune event
body produces antibodies against beta cells= destruction
what biomarker for insluin can no longer be detected after clinical onset of T1D
C peptide
over the course of T1D treatment, how has insluin origin chanegd
animal insluin -> human insulin -> synthetic insulin analogues
T1D: why is islet transplantation as a treatment difficult
high number of islets needed to replace them
not used commonly
what does a bionic pancreas do
- 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
