Flashcards in Biochemistry Deck (48):
1
What cells release glucagon?
alpha cells
2
What are the 4 types of endocrine cell in the pancreas?
beta cells; alpha cells; PP cells; delta cells
3
What do the delta cells release?
somatostatin
4
What do the PP cells release?
pancreatic polypeptide
5
What is synthesised at the RER in beta cells?
preproinsulin
6
What are the 3 parts of the preproinsulin?
two polypeptide chains and a connecting peptide
7
what type of bonds link the two polypeptide chains?
disulfide bonds
8
What is the most rapidly acting insulin?
insulin lispro
9
What insulin is administered as a single bedtime dose?
insulin glargine
10
What is the graph of action for insulin glargine like?
a peakless prolonged action
11
What transporter does glucose enter the beta cells by?
GLUT2 transporters
12
What happens to glucose when it enters the cell?
it is phosphorylated by glucokinase and then undergoes oxidative phosphorylation
13
How many ATP are produced per glucose?
36
14
What is the function of ATP in the beta cell?
ATP inhibits the ATP-sensitivie K+ channel Katp
15
What does inhibition of the Katp channel lead to?
depolarisation of the cell membrane
16
What does depolarisation of the cell membrane result in?
opening of the voltage-gated caclium channels
17
What does the intracellular calcium do?
leads to fusion of secretory vesicles with the cell membrane adn release of insulin
18
Why is the release of insulin biphasic?
only 5% of insulin granules are immediately available for release, reserve pool must undergo preparation to become mobilised, if blood sugar is not stabilised by inital release
19
What are the 2 proteins taht form the Katp channel?
the pore subunit- Kir6 and the regulatory subunit-SUR1
20
Which part of the Katp channel does the ATP bind to?
Kir6 part
21
What class of drugs can bind to the SUR1 and inhibit the channel?
sulphonylurea
22
What drug stimulates the Katp channel?
diazoxide
23
What effect does diazoxide have?
inhibits insulin secretion as the membrane is not depolarised by keeping the K inside
24
What would Kir6 mutations that result in activated Katp channels or increase in Katp numbers result in?
neonatal diabetes (insulin wouldnt get released as no depolarisation)
25
What is MODY?
monogenic diabtes with genetic defect in beta cell function
26
What is the difference between type 1 diabetes and MODY?
type 1 is a loss of insulin secreting beta cells and MODY is a defective glucose sensing in the pancreas and/or loss of insulin secretion
27
What is type 2 diabetes?
intially hyperglcaemia with hyperinsulinamia then there is reduced insulin sensitivity in tissues
28
What are the biological effects of insulin?
amino acid uptake in muscle; DNA synthesis; protein synthesis; growth responses; glucose uptake in muscle and adipose tissue; lipogenesis in adipose tissue and liver. turns off lipolysis and gluconeogenesis
29
Is insulin an anabolic or catabolic hormone?
anabolic
30
On what group do proteins get phosphorylated?
hydroxyl group
31
What amino acids are able to be phosphorylated?
serine; threonine; tyrosine
32
Why does adding phosphate change the structure of the protein?
introduces a large negative charge into the protein structure
33
What is the insulin receptor made up of?
a dimeric tyrosine kinase- two extracellular alpha subunits with insulin binding domains and two transmembrane beta subunits
34
What bond links the alpha and beta subunits?
disulfide bonds
35
What does binding of the insulin to the receptor cause?
causes them to phosphorylate themselves (autophosphrylation thus actiavting the catalytic activity of the recetpor
36
What does the phosphorylated receptor then do?
phosphorylates the insulin receptor substrates
37
What do the phosphorylated IRS-1 proteins activate?
the Ras/MAPK pathway and gene expression; PI3K,PKB and glycogen synthesis
38
What does PKB do?
causes the translocation of GLUT4 receptors and glucose to enter the cell
39
What is the key mediator of insulin sensitivity?
adipose functionality
40
Wh is it believed that adipose functionality is the key mediatory of insulin sensitivity?
because seever insulin resistance occurs with obesity as well as with complete absence of adipose tissue
41
What is leprechaunism-donohue syndrome?
a rare autosomal recessive gene in the insulin receptor leads to severe insulin resistance
42
What are the developmental abnormalities associated with leprechaunism-donohue syndrome?
elfin facial appearance; growth retardation; absence of subcutaneous fat, decreased muscle mass
43
What is rabson medenhall syndrome?
rare autosomal recessive genetic trait that causes severe insulin resistance hyperglycaemia and compensatory hyperinsulinaemia
44
Where are ketone bodies formed?
in liver mitochondria
45
What are ketone bodies derived from?
from acetyl-CoA from beta oxidation
46
What are ketone bodies used for in the body?
important molecules of energy metabolism for heart muscle and renal cortex
47
What causes the acidosis in ketone production?
they form acid in the blood and the high glucose excretion causes dehydration which exacerbates acidosis
48