In general we induced nicotamide first which will be followed by streptozotocin after 15 mins to induced diabetes in rats. but i would like to know if we reverse the process. what about their mechanism of action.
The animals will most likely die if you inject streptozotocin alone or before Nicotinamide. Or more accurately, they will have a much higher percentage of death- more than 50%.
Nicotinamide is the protective agent against 'too much toxicity' by streptozotocin. Same kind of toxicity happens with Aloxan. So, the combination of Nicotinamide and streptozotocin makes a very nice model for diabetes.
BTW, you should know that streptozotocin does not cause diabetes in Humans, so researchers who handle that chemical are relatively safe. streptozotocin is still toxic at higher doses in humans.
Regards
Nurul:
"The animals will most likely die if you inject streptozotocin alone or before Nicotinamide."
It all depends on the dose of STZ.
At an appropriate dose of STZ, when used correctly, animals do not die without nicotinamide.
STZ alone is what I have personally used to induce diabetes in rats on several occasions. It is either dissolved in citrate buffer or ice-cold saline. In my experience, I have had up to 80 percent successful induction with ZERO mortality by using ice-cold saline. You need to pick the appropriate dose, otherwise, animals will die due to its general toxicity; administering a shot of oral dextrose shortly after STZ injection also improves survival.
Tausif:
Yes, if the dosage can be carefully determined then many animals will survive although still some animals may die (10-20%). But why live with this guilt when you can have almost 100% survival with nicotinamide+ streptozotocin?
Regards
I do agree with both dear Tausif and Nurul regarding the use of STZ as nicotinamide in rats for the purpose of induction of diabetes.
Nurul:
"Yes, if the dosage can be carefully determined then many animals will survive although still some animals may die (10-20%)."
Statements without adequate details are not very useful and invariably inaccurate. Obviously dose of STZ is important and should be determined for specific strain of animal in question. But the of dose of STZ relates to a specific goal that one wishes to achieve in terms of severity of diabetes - proportion of beta cells destroyed immediately, effects of which are evident within a day.
As for 10-20% death, once again, without time frame, the statement carries no meaning. If the target is 100% (or very close to it) destruction of beta cells, at the correct dose no animal dies within a day or two - and all of them should die within a few months in the total absence of insulin.
I tend to use STZ alone, the effects of which are usually observed within a day or two post STZ injection. However, this may vary depending on the severity of diabetes which you wish to induce in your animals as explained by Tausif. I do however recommend titrating STZ in your model to determine a dose that works best for what you are trying to achieve.
I use 190mg/kg STZ in citrate buffer to induce moderate-severe diabetes in NOD/Scid mice, afterwhich ~80-90% of injected animals develop hyperglycaemia (>15mmol/L) within 2days, reach 25-35mmol/L within a week, and maintain this severity of diabetes until euthanasia. I do no treat with exogenous insulin. During this time, they remain as active as their normal counterparts, but display increased frequency of urination. After a few weeks to a month with chronic hyperglycaemia, they begin to develop abdominal swelling which is the time at which I euthanize the animals. If the animals are not euthanized, they die after a few months. Most animal ethics frameworks do not allow for this, which is why I euthanize early.
Dear,
In the majority of experiments, NA is given to rats 15 min before STZ to induce NIDDM in rats.... Why?........Administration of the diabetogenic dose of STZ to rats causes a decrease in body weight; however, this is attenuated by pre-treatment of animals with NA. Numerous studies have also demonstrated that the STZ-induced increase in blood glucose is significantly blunted when NA is administered prior to STZ. The advantageous effect of NA on blood glucose is due to the protection of B-cells against demage of STZ and is accompanied by increased blood insulin.
The severity of diabetes in experimental rats strongly depends on the doses of STZ and NA given to these animals.
Moreover, at an appropriate dose of STZ, rats survive without NA.
Regards
i injected i65mg /Kg of STZ dissolved in citrate buffer to wistar rats (10 animals) , and it was without inducing NA before .....there did'nt die but 2animals only /10 that exhibit hyperglycemia ....i mean more 150mg/L.....what should i do ....could i re inject another doses....please i need your help.....
REGARDS
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