Flashcards in Biochemistry of Insulin Deck (43):
Which cells secrete insulin?
Which cells secrete glucagon?
Which cells secrete somatostatin?
Which cells secrete pancreatic polypeptide?
Where is insulin made?
RER in b cells of pancreas
What is insulin synthesized as?
larger single chain preprohormone called preproinsulin
What chains does insulin contain?
2 polypeptide chains, linked by disulphide bonds
Why is human insulin now used?
to avoid problem of antibody formation
What is the glucose sensor which leads to insulin secretion?
How does glucose enter b cells?
through GLUT2 glucose transporter
What phosphorylyses glucose?
What does a change in glucose concentration lead to?
dramatic change in glucokinase activity
Increased metabolism of glucose leads to what happening to intracellular ATP?
What does ATP do to the KATP channel?
What does inhibition of KATP lead to?
depolarisation of cell membrane
What does depolarisation of cell membrane result in opening of?
How does an increases in calcium concentration in the cells cause insulin release?
leads to fusion of secretory vesicles
What is release of insulin in terms of phases?
Why are there two phases of insulin?
5% of insulin granules immediately ready for release
Reserve pool must undergo preparatory reactions to become mobilised and available for release
Which proteins do KATP channels consist of?
KIR6.1 (inward rectifier subunit, pore)
SUR1 (sulphonylurea receptor, regulatory)
What type of structure is the KATP channel
Are both proteins (KIR6.1 and SUR1) required for a functional channel to form?
Which class of drugs directly inhibits KATP?
sulphonylureas eg glibenclamide, tolbutamide
What is KATP stimulated by?
What does diazoxide do to insulin secretion?
What causes MODY?
mutations - genetic defect in b cell function
What type of diabetes is MODY?
familial version of Type II
What do HNF transcription factors and MODY play a key role in?
pancreas foetal development and neogenesis
regulate beta cell differentiation and function
What allows for differentiation between type 1 diabetes and MODY?
robust genetic screening - means MODY can be treated with sulphonylurea rather than insulin
loss of insulin secreting beta cells?
type 1 diabetes
defective glucose sensing in the pancreas and/or loss of insulin secretion?
Initially hyperglycaemia, with hyperinsulinaemia, so primary problem is reduced sensitivity in tissues?
Type 2 diabetes
What type of receptor are insulin receptrs?
What provides for a reversible method for altering protein function?
What can proteins get phosphorylated onto?
any hydroxyl group, introduces large negative charge into protein structure
What is the insulin receptor?
a dimeric tyrosine kinase
Name a rare autosomal recessive genetic trait with mutations in the gene for insulin receptor causing growth retardation, decreased muscle mat, no subcutaneous fat and elfin facial appearance?
Which autosoma recessive trait causes severe insulin resistance, hyper glycaemia, developmental abnormalities and acanthosis nicrigans?
rabson mendenhall syndrome
Where are ketone bodies formed?
What organs are ketone bodies important molecules of energy for?
What does fatty acid oxidation yield?
What can accumulation of ketone bodies lead to?