It is generally believed that STZ(40-70mg/kg, single dose) produces diabetes similar to type 1, which accounts for only 5-10% of diagnosed cases of diabetes(according to WHO& NIH). I observed from literature that most of the diabetes studies used this model. Why spend so much effort and attention on 5%? Would the use of type 2 model not be more appropriate, relevant and logical, since the results will address 95 rather than 5% ?
Dear Olorunfemi Eseyin
The attached article may be helpful to you
On the high end of that range, massive beta cell destruction predominates and the disease is indeed characteristic of type 1. On the lower end of that range, the effect is more moderate and somewhat characteristic of type 2, although without changes in insulin sensitivity. The model is very easy to initiate though, which ultimately, I would say is the answer to your question.
Neonatal STZ administration results in a disease phenotype that more resembles type 2 as the animal matures, but this takes several month. High fat feeding can also induce obesity and reduced glucose tolerance in some animal models, although not always insulin resistance, and beta cell failure is often absent. This model also takes several months to initiate. There are surgical models as well, again though, requiring more time and the development of surgical skill.
In short, there really exists no great model of type 2 diabetes in rodents. A moderate, one-time STZ injection is easy, and is no more difficult to defend that any of the other models.
Dear Olorunfemi Eseyin
The attached article may be helpful to you
The article is of interest, but does not mention the best models of T2DM: the obese diabetes prone rat strains such as Zucker. What I find fascinating about these strains is that the original animals were obese but did not develop diabetes. The diabetic strains were established by inbreeding within these obese animals selecting for diabetes. So they replicate remarkably the epidemiology and pathophysiology of human T2DM. Most obese individuals do not develop diabetes. Add the wrong genes to obesity and diabetes develops. STZ, even low dose with feeding, does not get close to reproducing this.
The contention that stz induces exclusively a diabetes of Type 1 is not completely accurate...STZ induces beta cell damage along with other side effects...There is almost no easy way to induce a model of type 2 diabetes in rodents since they only live a year or two (plus you have to complete your project in three)..and in humans it takes years to develop glucose intolerance and beta cell loss. So to facilitate this process scientists use stz to induce beta cell damage...I am not going to reiterate monogenetic models or multi genetic models of type 2 diabetes in rodents since all the literature is out there for your to reach, however, whether you use stz in newly born rodents or obesity induced type 2 diabetes, the sole purpose is to induce beta cell damage and insulin deficiency..Having said that stz also induces insulin resistance and glucose intolerance at low doses which is good for generation of non-obese models of diabetes...Monogenic models of type 2 diabetes do not require stz but they have their own pitfalls.. Considering the end stages of type 2 diabetes resembling that of type 1, it should not come as a surprise that stz is used to induce both type 1 or type 2 diabetes in some cases...
This is indeed a fascinating debate! I accept that STZ can be used to accelerate the onset of hyperglycaemic that is difficult otherwise to replicate in animal models. But T2DM is so much more than hyperglycaemia. I guess what is important is the question we are asking and accordingly the model we need. If all that is important is the hyperglycaemia then I guess STZ is useful. But the macrovascular disease of T2DM us at least as important as the microvascular disease. If this is of interest what should the model be? I do not know of any evidence showing improved glycaemic control to reduce macrovascular disease. The undoubted polygenic nature of T2 may be relevant here? The selective breeding of ZFDM rats may well be selecting for a constellation of genes replicating the polygenic nature of T2. Unproven, but intriguing and fascinating?
My concern is that we seem to keep missing the point. Stable moderate hyperglycaemia is not T2DM. There are many ways of producing this. There may be some situations where the impact of stable moderate hyperglycaemia is to be studied, and such models may then be appropriate. But this is not modelling T2DM. This is modelling one aspect of T2DM. So as argued before, the appropriateness of the model is determined by the hypothesis being tested. If we have clarity about this then the correct model will be used.
Always the cynic, I wouldn't be at all surprised if money didn't have something to do with it. Have you priced out ZDF rats lately? They are more than 10 times the cost of a Wistar. I think that using the lower dose STZ model can be used, it depends on what question you are asking.
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