hello, I recently was trying to make type II diabetic rats model by i.p injection STZ (65mg/kg). But the rats was dying in 5 days even I tried to give little insulin(4 IU) everyday since day 3 to control the deteriorated rats (blood glucose > 25) . Am I missing some important issue during performing animal model and how to increase the survival rate? Could anybody give some advice on this?
Hello Hong Huang,
You could check if the age, gender and rat strain was comparable with your reference literature. As with many things, it seems that strains react differently. I found this related article here on Research Gate: Induction of Diabetes Mellitus in Rats Using Intraperitoneal Streptozotocin: A Comparison between 2 Strains of Rats, and information on another rat strain on PubMed: PMID: 10703720.
Maybe you could use a milder model as described here with feeding high fat diet and administering low doses of STZ: PMID: 15979893.
It doesn't seems right to me (scientifically and ethically) to induce such a severe condition that animals die from it. I guess you agree, as you can't do much with a dead animal.
Best, Laura
you can reduce the stz dose, instead of a single dose give 2-3 small doses to destroy the pancreatic beta-cells.
I have experience with streptozotocin-induced diabetes using young, male Sprague Dawley rats. We would give a lower dose (55 mg/kg) via tail vein injection. In nearly every case each rat was diabetic within 2 days after only one administration of STZ - BG between 400-500 mg/dL. Another thing you may want to be sure you adjust the pH of your vehicle buffer very carefully (sodium citrate 0.01M, pH 4.5).
The dose is a bit high. Most people use 60 mg/kg or less to induce Type 1 diabetes. You really cannot induce true Type 2 diabetes in a rat model using STZ.
I concur with John H Mcneill, using STZ to create a model for type 2 diabetes is not a good idea. There are known models of type 2 diabetes that you could use, such as Zucker Fatty/fatty.
Since type 2 diabetes is not a uniform disease and it's more of a syndrome so it all depends on what aspects of type 2 diabetes you are interested, and based on that, you could pick the best possible model... or generate one.
As for the high mortality of rats within 5 days after injecting (ip) only 65mg/kg STZ, it should not happen but it is difficult to know the cause without additional details from you.
1. Do they die of hypoglycemia on the first day (immediately after destruction of beta cells, animals can become transiently hyperinsulinemic and consequently hypoglycemic)?
2. Do your rats look obviously dehydrated; do they have unrestricted access to water?
3. Are they adequately active, eating drinking, grooming etc.?
I am curious why you were giving insulin. Usually during the period of time that STZ is killing beta cells, there is a lot of insulin released from the dying beta cells and a tendency for hypoglycemia. You did not state you units for blood glucose, so either the level is very high (mmol/L) or very low (mg/dL). Did you give glucose in the water while the rats were recovering from STZ? What method did you use to determine BG?
In any event, I agree wholeheartedly with those who wrote above in favor of looking for another model. STZ does not create anything resembling T2D. You are wasting time and money on such an aproach, especially if your animals die, unless you have a very compelling reason for using STZ in this manner.
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