Compare blood glucose levels after fasting in young control mice and young IKO mice without FoxO1.

Aging and having pregnancies are considered to be physiological stresses. Deduce the effect of stress on blood glucose levels.

Outline the relationship between blood glucose levels after fasting and lack of FoxO1 in the mice studied.

Calculate the percentage difference in β cell mass of the IKO mice compared to the control mice.

State the correlation between lack of FoxO1 and pancreatic hormones in mice.

State which group of cells showed the least change in the mice studied.

Deduce the effects of aging on the distribution of cell types in mice.

A hypothesis has been suggested that diabetes is caused by β cells losing their ability to act as β cells, not by the death of β cells.  In other words they dedifferentiate.

Using all the information provided, discuss whether the data support this hypothesis.

When there are high blood glucose levels, more FoxO1 is found in the nucleus of the cell than in the cytoplasm.  Suggest a role of FoxO1 considering this and the data.

similar/same/nearly same (means)/very small difference/both at a low level;
means/averages (all) close to 0.8 mg ml^–1;
differences not (statistically) significant;
similar/same/nearly same range/spread of data;
All marking points are comparisons between control and IKO mice. Do not award marks for comparisons between male and female mice.

stress causes increase (in mean blood glucose/sugar);
older mice/males/females / aging mice show the increase;
Reject answers that only compare control and IKO mice or only compare male and female mice.

in young mice/3 month old mice lack of FoxO1/IKO/fewer beta cells does not affect/has little effect on blood glucose/sugar;
in older females/aging males blood glucose/sugar (much) higher with lack of FoxO1/IKO/fewer beta cells;

Award [1] for an answer:
accept either 35 / 34.8 / 34.78 (this answer may be expressed as a negative) OR 53 / 53.3 / 53.33;
Do not award the mark if more than two decimal places shown or if the answer is incorrectly rounded up or down.

Award [1] for working, accepting any of the following:

lack of FoxO1 (correlates) with low/decreased insulin and high/increased glucagon levels.

newly formed β cells
Accept if newly formed beta cells in IKO mice but not in control mice only.
Reject all answers apart from the first given and any comparisons between IKO and control mice, rather than between younger and older mice.

All marking points are deductions based on comparing older females with 3 month females and on the assumption that any changes in % are due to aging.
newly formed β cells fewer/reduced/smaller % (in control/IKO mice);
cells still producing insulin (slightly) more/increased/higher % in controls;
cells still producing insulin fewer/reduced/smaller % in IKO mice;
cells no longer producing insulin only in older IKO mice;
Accept answers where IKO mice are referred to as mice without FoxO1 and control mice are referred to as mice with FoxO1.

supported in older IKO mice/older mice lacking FoxO1 by:
cells no longer producing insulin present (only) in older IKO mice/mice lacking FoxO1;
(type 2) diabetes/high blood glucose/lower insulin in older IKO mice/mice lacking FoxO1;

not supported by:
lower mass of β cells in older IKO mice/mice lacking FoxO1;
no drop/small rise/small change in cells producing insulin in older control mice;

Candidates must make it clear in their answer to (h) whether the data is in support of the hypothesis or against. Evidence can be included for and against.
Answers should specify whether the data is from older IKO mice or from older control mice. If the age is not specified in the answer, penalise for one of the marking points but not any others.

promotes transcription of/expression of genes;
for differentiation/growth/mitosis/cell division in β cells / for making insulin;

represses transcription of/expression of genes;
for making glucagon;

This proved to be quite a discriminating first question with relatively few candidates scoring both marks. There were two common faults in answers: comparing males and females rather than control and IKO mice and describing very small differences in means as though they were significant. Candidates should be encouraged to pick out significant trends from data and here it was that the four means being compared were all almost the same.

Answers to this question were very varied and as in the previous question, some candidates made the wrong comparison. Here the comparison should have been between young and old mice, not between males and females or IKO and control mice. The data showed significantly higher blood glucose concentrations in older mice than in younger, leading to the deduction that stress increases blood glucose levels.

Generally candidates fared better here, with most making the correct comparison of IKO with control mice. However, the data showed a clear difference between younger and older mice and answers were expected to include it. As in (a) some answers did not distinguish between significant and insignificant differences. The mean in young females was higher in the IKO than the control groups but the difference was insignificant so it was not appropriate to say that all IKO means were higher than controls except in young males.

The wording of this question proved to be ambiguous, so a mark scheme was devised that allowed any valid interpretation and method of calculation. About half of candidates calculated one of the accepted answers. Marks were lost unnecessarily by some candidates, either for not showing any working, or for rounding up or down the answer in the wrong direction.

There was some concern among teachers that it is not possible to deduce a correlation from present/absent data, but candidates mostly did not have difficulty understanding what was expected here. A very common mistake was to give an answer for pancreatic hormones in general rather than for insulin and glucagon separately as was essential because the lack of Fox01 had opposite effects on the two pancreatic hormones.

About half of candidates answered this question successfully. To answer it correctly candidates had to realise that the change referred to was between the younger and older mice and that the answer had to be valid for both control and IKO mice as neither was specified. A common error was to answer with a type of mouse, such as older females rather than a group of cells.

This question was generally well answered with candidates able to make at least one and sometimes two valid comparison between the percentages of cell types in younger and older mice and thus what the effects of aging are. For most of the answers it was necessary to specify either control or IKO mice as the trends were different.  

This question was intended to encourage candidates to bring together conclusions from the various data sources in the question, in order to evaluate a hypothesis. For nearly all candidates this proved to be too hard a task. Nevertheless, many candidates made some valid points and these were rewarded with marks. As so often in discussing a hypothesis there were valid arguments both for and against the hypothesis.

Candidates found this question very difficult and only a small number were able to use the information in the stem of the question about Fox01’s role as a transcription factor, together with the effects of a lack of Fox01 shown by the data in the question, to suggest a possible role.