insulin prof sukhi bansal

how do advanced glyction end products AGEs form?

excess glucose can react with proteins and tissues

what are some some consequences of AGEs in the body?

can create inflammatory conditions in the vasculature, heart, kidney, eyes, nerves and skin

describe the chemical synthesis in formation of a glycated protein?

glucose has an aldeyde bond which reacts with the amine on the protein, this undergoes amidori rearrangement to form a glycated protein

what can happen as a result of glycated haemoglobin?

modifies the structure so can longer carry oxygen

why do patients with type 2 diabetes have high glucagon?

insulin is unable to suppress glucagon due to resistance

how many chains does insulin have and what connects them?

2 chains, A and B that are connected with disulphide bridges

what is the disulphide bridge formed with?

two cysteine residues, that contain thiols which are oxidized to form a disulphide bridge

what enzymes catalyses the oxidation of the disulphide bridges?

portein disulphide isomerase

what can happen to the structure of insulin as the pH increases?

it can form aggregates

what is the first compound in insulin synthesis?

pre pro insulin

what happens to the pre pro insulin once it is in the ER lumen?

the signal sequence of the peptide is cleaved giving pro insulin

why is the signal sequence cleaved?

it contains amino acids that are highly basic or hydrophobic so to get through the membrane they are cleaved

what happens to pro insulin after the cleaving of the signal sequence in the golgi?

folding occurs due to the 3 disulphide bridges and it forms a hexamer with zinc

in the golgi what happens to pro insulin to form mature insulin?

the c peptide is cleaved to form mature insulin which is packaged in a secretory vesicle

describe the different types of disulphide bridges that can from?

two intramolecular and one intermolecular between the two chains of insulin

how does the trypsin like enzyme cleave the c- peptide?

the enzyme is selective for double charged amino residues

why does conversion from pro insulin to insulin make the peptide percipitate?

removal of all charges amino acid residues makes the peptide insoluable.

which amino acid residue allows the formation of the hexamor with zinc

histadine

what happens to the concentration of insulin going from the vesciles to the blood in units?

goes from millimolar to micromolar

how does insulin dissociate from the zine hexamer into the blood?

in the blood the concentration of insulin falls which causes it to dissociate from the hexamer, and is released as a monomer

what type of insulin is closest to humans?

porcine

how can protamine- a basic protein-be used to increase the duration of insulin in formulations?

protamine binds insulin as it has a net 2- charge. this means that insulin will slowly come of the protamine increasing the duration

how can increasing the concentration of zinc in insulin formulations increase their duration?

higher concentration of zinc will mean that the hexamer formed will be stable for longer, so the insulin will slowly come off and increase the duration.