Practice questions Flashcards
Patients with diabetes control their blood sugar levels with daily insulin injections.
Draw a diagram of the molecular signalling cascade by which insulin promotes glucose uptake in adipose tissue.
Glucokinase is a key enzyme that functions as a glucose sensor in the pancreatic beta-cell.
What reaction does glucokinase catalyse? (1 mark)
Glucose to glucose-6-phosphate (1 mark)
Glucokinase is a key enzyme that functions as a glucose sensor in the pancreatic beta-cell. Describe two key characteristics of the enzyme that enable glucokinase to set the threshold for glucose stimulated insulin secretion. (2 marks)
Low affinity for glucose (S0.5 8-10mM) - ensures only secrete insulin when glucose levels increase above basal (1 mark)
lack of inhibition by product (glucose-6-phosphate) - insulin secretion continues for as long as high glucose levels maintained(1 mark)
In order to reduce the number of insulin injections scientists have been working to develop a ‘smart’ insulin that would only need to be taken once a day.
Describe the features that a ‘smart’ insulin would require to effectively maintain blood glucose levels over 24hrs. (2 marks)
Properties:
Be inactive when blood glucose levels are low/normal (1 mark)
Rapidly activated when blood glucose levels rise (1 mark)
Activation rapidly stopped when glucose levels fall (1 mark)
(any 2 points for max 2 marks)
In order to reduce the number of insulin injections scientists have been working to develop a ‘smart’ insulin that would only need to be taken once a day.
Describe a potential strategy that could be used to achieve this. (2 marks)
Strategy:
Any feasible suggestion
e.g. microneedle array patches – insulin contained in polymer that dissociates in hypoxic environments –i.e. when blood glucose levels rise – polymer dissociates and releases insulin
or
Modified insulin molecule – albumin binding region + glucose sensor - glucose only released from albumin when glucose levels are high
Identify FOUR types of social prescription.
Model Answer: Any four of the following…
arts on prescription,
museums on prescription (or heritage programs),
exercise referral (or exercise on prescription or green prescriptions),
bibliotherapy (or books on prescription),
time banks,
education on prescription,
green gyms (or ecotherapy).
5
Robert’s PhD research involves discovery of new drugs to treat lung fibrosis, and he wants to test the efficacy of a candidate drug in a suitable animal model.
Give ONE example of a rodent model of lung fibrosis. (1 mark)
Example of model of lung fibrosis:initiated by: bleomycin, FITC, radiation-induced, adenoviral-TGFbeta, silica, transgenic mice, viral exacerbation (e.g. gammaherpesvirus) (1 mark for any correct answer)
Robert’s PhD research involves discovery of new drugs to treat lung fibrosis, and he wants to test the efficacy of a candidate drug in a suitable animal model.
Describe THREE aspects of experimental lung fibrosis models which make them good (or bad) for pre-clinical drug evaluation. (3 marks)
Pros and cons of animal models:
Complex systems, allowing assessment of interaction between different cellular compartments, organs, immunity etc, which cannot yet be modelled by in vitro experiments. Use of transgenics/knockouts to understand role of specific genes.
Easy to administer damaging insult, and quick to develop fibrosis.
May be clinically relevant (e.g. bleomycin causes pulmonary fibrosis in humans).
Modelling of pharmacokinetics and pharmacodynamics for pre-clinical drug testing.
Fibrosis may or may not be persistent, and is rarely progressive (unlike the human disease).
Fibrosis may resolve (unlike the human disease).
Models do not recapitulate all of the histological features seen in the human disease (e.g. fibrotic foci).
Majority of models are driven by inflammation (which may not be the case in human lung fibrosis).
There are many fundamental differences between mouse and man (genetically, immunologically, anatomically etc etc).
Majority of studies are performed in young mice (for pragmatic reasons), but lung fibrosis is a disease of ageing.
Discrepancy between results from animal models and results from clinical trials (therefore not clinically-predictive anyway!).
Different outcomes in different strains of mice.
+ any other reasonable answer
A child has been diagnosed with pseudohypoaldosteronism type II (PHA II) caused by a mutation of the Cullin 3 gene and is about to commence a new form of PHA IItreatment.
State the current established treatment option for PHA II and explain its mechanism of action. (2 marks)
Established treatment –
thiazides (1 mark)– control hypertension in part by inhibiting reabsorption of sodium (Na+) and chloride (Cl−) ions from the distal convoluted tubules in the kidneys by blocking the thiazide-sensitive Na+-Cl− symporter. (1 mark)
A child has been diagnosed with pseudohypoaldosteronism type II (PHA II) caused by a mutation of the Cullin 3 gene and is about to commence a new form of PHA IItreatment.
Describe TWO potential new treatments option for PHA II, including the molecular targets. (2 marks)
New
WNKs kinases and the relative kinase inhibitors (1 mark)
or
SPAK/OSR1 kinases and the relative kinase inhibitors (1 mark)
or
Inhibitors that disrupt WNKs and SPAK/OSR1 binding (protein-protein interaction)(1 mark)
(max 2 marks)
Many patients with type 1 diabetes develop autoantibodies to selected islet proteins prior to the onset of clinical symptoms.
Explain why such antibodies are produced and indicate whether you consider that they play an important role in the disease process?
Score: (3 marks)
Why produced:
Islet autoantibodies are produced against a small number of proteins(insulin, glutamate decarboxylase, a tyrosine phosphatase and a zinc transporter)suggesting that these antigens are aberrantly processedand presented to the immune system during the process of islet autoimmunity (1 mark).
Role in disease process:
However, such antibodies are not directly pathogenic (1 mark)and they are likely to be markers of disease rather than causative agents (1 mark). Some people (especially close relatives of patients with type 1 diabetes) will develop such autoantibodies without ever getting type 1 diabetes. (1 mark)
Describe the steps by which DNA methylation is measured in the lab.
1 mark= DNA is treated with sodium bisulfite
1 mark= Sodium bisulfite converts unmethylated cytosines to uracil by deamination.
1 mark= The uracil is then converted to thyamine by PCR (or another whole genome amplification method).
1 mark= The bisulfite converted DNA can then be used for various different sequencing / array based technologies eg pyrosequencing, Illumina 450K DNA methylation arrays, bisulfite whole genome sequencing.
(max 3 marks)
Immune-modulators are one of the key areas being developed for the treatment of traumatic brain injury.
Discuss why histone deacetylase (HDAC) inhibitors could potentially be used for treatment of traumatic brain injury. (4 marks)
These HDAC inhibitors preferentially upregulate the transcriptional expression of many neuroprotective genes (1 mark)involved in cell survival, proliferation, and differentiation (1 mark).
Both grey matter and white matter tracts are significantly preserved by HDAC inhibition after TBI. (1 mark)
HDAC inhibitors suppress inflammatory responses (1 mark), promote neurogenesis(1 mark) and stimulate axonal regeneration (1 mark).
Immune-modulators are one of the key areas being developed for the treatment of traumatic brain injury.
Name one example of an HDAC inhibitor that has already been approved for clinical use. (1 marks)
Example: Valproate or vorinostat (1 mark for either)
