Practice Questions Flashcards
What is the molecular signalling pathway by which insulin increases glucose uptake in adipocytes?
Insulin bind to tyrosine kinase receptor
Dimerisation and transautophosphorylation
Phosphorylation of IRS1
IRS1 recruits SH2 domain of PI3K, activating it
PI3K phosphorylates PIP2 into PIP3
PIP3 recruits PDK1 and Akt (PKB) to the membrane
PDK1 phosphorylates Akt
Akt inhibits AS160
Vesicles containing GLUT4 transporters translocate to the membrane
Also activates glycogen synthase
What reaction does glucokinase catalyse?
Glucose –> glucose-6-phosphate
First step of glycolysis
Uses ATP
What characteristics of glucokinase allow it to set the threshold for insulin secretion?
Low affinity for glucose
Not inhibited by product at high concentrations
Describe the features of a smart insulin that would be able to regulate glucose levels for 24 hours
Only be released when blood glucose levels are high
Release the appropriate amount of insulin proportionate to blood glucose levels
Name all the possible rodent models of lung fibrosis
Bleomycin model Full body irradiation dose Silica mineral fibres exposure Transgenic mouse model FITC administration
What aspects of experimental lung fibrosis models make them bad for drug evaluation?
In bleomycin mice the fibrosis is reversible, whereas in humans it is not
In bleomycin mice the lesions are bronchiolocentric rather than in the alveoli
The method used to create the disease is not the same pathogenesis as in humans
Cannot take into account human genetic predispositions
Metabolic/systemic differences to humans
What is the established treatment for PHA II and how does it work?
Thiazide diuretics Antagonists of the NCC cotransporter Reduces NCC activity and lowers Na+ and Cl- reabsorption Lowers water resabsorption Lowers BP
Name two potential future treatments for PHA II and their molecular targets
SPAK specific ATP competitive kinase inhibitors
Target the SPAK protein
