Biochem Flashcards
(25 cards)
function of beta cells
secrete insulin
function of alpha cells
secrete glucagon
function of delta cells
secrete somatostatin
function of PP cells
secrete pancreatic polypeptide
describe the production of insulin
synthesised in the rough ER of beta cells as preproinsulin
cleaved twice to form insulin + C-peptide
C-peptide is secreted along with insulin and is a waste product which can be measured to assess insulin levels
describe the secretion of insulin
glucose enters the beta cell via GLUT2 phosphorylated to glucose-6-phosphate by glucokinase metabolised to produce ATP closes K-ATP channels depolarises cell membrane Ca2+ channels open secretory vesicles fuse with cell membrane insulin is released
potassium channels consist of which 2 proteins
inward rectifier unit (Kir) which is the pore subunit sulphonylurea receptor (SUR1) which is the regulatory subunit
what is the effect of a mutation causing overactive K-ATP channels
profound neonatal diabetes
what is the effect of a mutation causing inactive K-ATP channels
hyperinsulinaemia
what is MODY
monogenic diabetes with a genetic defect in beta cell function
familial early onset type 2 diabetes
primary defect in insulin secretion
mutation in MODY1
HNF-4a
mutation in MODY2
glucokinase
mutation in MODY3
HNF-1a
mutation in MODY4
IPF1
mutation in MODY5
HNF-1b
mutation in MODY6
neuroD1
what is happening in type 1 diabetes
antibodies which destroy the insulin secreting beta cells in the pancreas
what is happening in MODY
defective glucose sensing in the pancreas and/or loss of insulin secretion
what is happening in type 2 diabetes
hyperglycaemia with hyperinsulinaemia so primary problem is reduced insulin sensitivity in tissues
describe insulin signalling
insulin binds to alpha subunit of tyrosine kinase receptor
beta subunits are autophosphorylated
IRS is phosphorylated
IRS activates Ras/MAPK pathway and gene expression
IRS activates PI3K, PKB and glycogen synthesis
PKB stimulates GLUT4 translocation
glucose is taken up and cell growth is stimulated
what do kinases do
phosphorylation
which amino acids can phosphorylation occur on
serine
threonine
tyrosine
which bonds link the alpha and beta subunits of the insulin receptor
disulphide bonds
where are ketone bodies formed
liver mitochondria