We include the option for rats to take 2% sucrose in drinking water supplied to them approx 4 hours post injection (65 mg/kg i.p.STZ given to 300-400g rats) , in addition to their normal water, for the first 24 hours. In terms of affecting the STZ toxicity, I was under the impression that due to the rapid degradation of STZ, PK etc giving sucrose in this way would not really influence the toxicity of STZ, just provide some relief against the initial hypoglycaemia seen. I think the animal weight probably moreover their body fat helps them through the worst as well, as you see a rapid loss of body fat progressively throughout.

Hi,

I have used 10% w/v sucrose in drinking water for C57BJ6 mice for 7 days, in 5 days 60 mg/kg of STZ treatment. This helps to counteract the hypoglycemia.

Hi,

I have also used 10% w/v sucrose in drinking water for swiss, but this side effect has rarely appeared.

As people have said above, with the right dose of STZ I have not found this to be a problem. I guess significant hypoglycaemia is seen when the STZ dose is too high and liver damage is seen preventing counter-regulatory responses. Sucrose/glucose would of course work but might also affect STZ toxicity limiting beta cell kill resulting in a more variable incidence of sustained diabetes.

hi Maarten,

i have used distilled water in drinking water for mus musculus mice , that have no seen any side effect after that, and this did COUNTERACT the hypoglycemia,

that is new but successfully for it.

THANKS

Hi Bhaskar,

Correct me if I am wrong, but you are just giving them water then. Did you chose distilled water for a reason? I guess your mice just didn't develop a hypoglycaemia. Therefore I think you cannot speak of a counteraction, since there was no need for it in the first place.

Thanks

We include the option for rats to take 2% sucrose in drinking water supplied to them approx 4 hours post injection (65 mg/kg i.p.STZ given to 300-400g rats) , in addition to their normal water, for the first 24 hours. In terms of affecting the STZ toxicity, I was under the impression that due to the rapid degradation of STZ, PK etc giving sucrose in this way would not really influence the toxicity of STZ, just provide some relief against the initial hypoglycaemia seen. I think the animal weight probably moreover their body fat helps them through the worst as well, as you see a rapid loss of body fat progressively throughout.

I should be clear that I am not arguing against giving sucrose/glucose post STZ. However, given that STZ is taken up by GLUT2, glucose will act as a competitive antagonist for uptake. We looked carefully at plasma half life of STZ as the model I have worked with most is islet transplantation. We did not want the newly transplanted islets to be damaged by the STZ administered to induce diabetes. We consistently saw toxicity to newly transplanted islets 24h after STZ administration and possibly at 48h. We therefore did not transplant until day 3 post diabetes induction. Although the plasma half life of the alpha-anomer of STZ and the time to equilibrium and percentage alpha/beta anomers in physiological conditions have not clearly been defined (as far as I know) the de la Garza-Rodea paper that has been referred to elsewhere (attached) gives us useful information. You will see that degradation of STZ is slow. So I am sure that there is the potential for ongoing uptake and further toxicity. This paper would in effect seem to define a dose response curve. Consideration of table 1 in particular shows this with less mortality but lower incidence of diabetes with the equilibrated form. This is predictable from the data presented later as the dose of a-anomer will be significantly lower in the equilibrated solution. My argument is just to keep the model as simple as possible given the multiple variables we are trying to control. A lower dose of STZ without sucrose seems simpler, but (as I argued in my comparison with PCR elsewhere on RG!) if it works great. When the protocol doesn't work or you have practical constraints, as for Maarten, these details become very important. I should add that we allowed animals to feed normally after STZ administration.

I have always wondered if the fat loss (which we saw also) is due to STZ toxicity as it is very rapid?

One additional option is to switch out from i.p. STZ.

We use 50mg/kg i.v. (tail vein) STZ in our rats. They get a subcutaneous insulin implant at the same time, which obviously poses a risk for hypoglycaemia.

So for the first 24 hours they get a normal water bottle plus a 5% sucrose bottle and All I see is glucose going way up within 24 hours of STZ. Never hypoglycaemia.

To me this suggests that your hypoglycaemia could maybe be caused by the route of STZ administration.

ip is pharmacokinetically almost indistinguishable from iv. Main problem is good technique to avoid injection into bowel. This is a red herring that often comes up in these discussions. I would suggest you simply have the right dose of STZ in your model in your hands!

Richard that is a very good point. Since i.v. has been so reliable for me I never considered that possibility in the case of i.p. However, repeated injections of STZ are usually necessary for i.p. whereas only one injection is necessary when i.v. is used. That seems consistent with a more efficient delivery when i.v. is used to me.

Single ip injections work very well too!

I think its better to give glucose with little salt in it..absorption will be good.. After 6 hr of streptozotozin injection u can give glucose dose orally..its better to select dose in the proportion to body weight..5-6 gm/kg body weight may work..

Richard,

I agree with your assessment of STZ. I am guessing the the weight loss that you see is due to the animals being uncomfortable and therefore not eating much in the initial days after STZ treatment. Remember that rodents have fast metabolism in general and will easily lose 4-8% of their body weight during an overnight fast. If a rodent continues to lose weight beyond 3 days I would consider sacrificing it, or if the weight loss is believed to be caused by diabetes and not collateral damage from the STZ, treat the diabetes to minimize excess weight loss.

If untreated diabetic controls are needed in a study, which is often the case, giving them insulin is not a realistic option. We have an established set of standards in our institution (I am sure it is true for most places) which consider the general health of animals in conjunction with the body weight before triggering an automatic euthanasia.

Question:

Can I inject 7% Sucrose solution by IV to human?

Do you expect any side effect

care is of essence during the induction of diabetes with strep to avoid unnecessary deaths. Careful calculation of weight of both animal and strep is very importaant.