Diabetes and Drug Targets Flashcards
what is gestational diabetes
pregnant women whom have not been previously diagnosed with diabetes exhibit high levels of blood glucose sugar
what is the cause of gestational diabetes
occurs in the third trimester due to changes in renal absorbtion
what do alpha/beta cells in the ilses of Langerhan release
beta - insulin
alpha - glucagon
what is a unique feature of the pancreas
it is an endocrine and exocrine organ
what does insulin bind to
the insulin receptor
what can conformational change of the insulin receptor cause
convert glucose to glycogen
convert glucose to pyruvate - converted into fatty acids
if there is a quite high blood glucose sugar level, what can the conformational change in insulin receptor cause
intracellular vesicles - glucose transporter-4 can fuse to the membrane to uptake more glucose to be converted into glycogen/fatty acids
what is the function of the hydrophobic terminus of insulin
prevents it from escaping the ribosome into the cytoplasm
what is the function of the translocon in terms of insulin production
recognises the signal sequence of insulin and allows it to enter the ER lumen
then it cleaves the signal sequence
what is the pH of the ER lumen, Golgi apparatus and secretory vessels
ER lumen - 7.2
Golgi - 6-6.7
secretory vesicles - 5.7
why is the gradual decrease in pH from ER to vesicles important in insulin secretion
the pI (overall charge) of insulin is 5.1
if the pI is close to the pH it will precipitate out of solution - controlled manner
can be reversed
how is mature insulin packaged
into a zinc-bound monomer
a hexagonal shape with 2 zinc and 6 insulin
how is zinc introduced for packaging and why is it a risk factor
Znt8 is a Zn+2 transporter
in Type 1 diabetes it will recognise Znt8 as a foreign protein and destroy it
what are the 3 states in which insulin hexamers can exist
R6
T6
T3R3
what was used in the formation of R6 crystals and why, and why is it not in use anymore
phenol was used as an antibacterial agent in R6 preparation
not used anymore because it is toxic
what plays an important role in the chemical and physical stability of insulin
the intrinsic flexibility at the ends of the B chains
what is a function of the hexameric packaging of insulin
stabilises insulin and prevents degradation
what are additives to insulin hexamers
protamine
phenols/metacresol
zinc chloride
what is the function of protamine for insulin hexamers
a protein extracted from fish sperm nucleus
regulates interactions between hexamers and dimers
slows the release of insulin
function of zinc chloride for insulin hexamers
stabilise the hexamer
zinc ions are the predominant quaternary structure of pharmacological insulin
what are the 3 general forms of insulin
fast acting analogous
slow acting analogous
very slow acting analogous