July 14, 2008

Why Rodent Diabetes Research is Irrelevant

Week in and week out we read articles about obese mice and rats with "type 2 diabetes" claiming that this or that treatment cures them and suggesting that a similar cure for people is just around the corner.

Nothing could be more wrong.

The usual reason for urging caution with rodent studies is that rodents have very different pancreatic function than do primates. In fact, much about their metabolisms is very different from ours.

But the reason that rodent studies are usually a dead end goes much further than that. The real reason is that while these rat and mouse "models" for Type 2 diabetes have elevated blood sugars and the OB mouse is, indeed, very fat, the genetic flaws that cause the high blood sugars and obesity in these rodents are not flaws in the genes that have been connected with diabetes in human populations.

The OB mouse, for example, is leptin deficient. Only a few families of humans world wide are obese because of leptin deficiency. Still, researchers continue to use OB mice to study obesity, though the underlying differences in metabolism of the OB mouse and the obese human are as different as those of a person who is coughing because they have TB and a person coughing because they have COPD.

The rat model for type 2 diabetes is the GK Wistar rat. Studies of which genes are defective in these rats turned up genes researchers named Niddm1 and Niddm2, which sound impressive until you note that neither of these gene mutations are commonly found in humans with Type 2. In fact, the only way that scientists have been able to study any of the gene abnormalities that are known to be common in humans is to breed transgenic mice that have had human genes inserted into them! (You can read about one such experiment HERE).

Nevertheless, nutrition researchers and researchers investigating all kinds of diabetes related issues continue to experiment on the common mouse and rat models for diabetes--the ones with defective genes not found in humans that are handy for researchers because they breed true.

And they continue to come up with findings that have little or no relevance to humans.

Even the argument that these rodent models are useful for studying the effects of high blood sugar on the organism are suspect because the organism in question is so metabolically different from humans. And because we don't know how much of what we are seeing is the result of the high blood sugar or of some other effect of the grossly abnormal non-human genes that give us a rat or mouse that will breed reliably diabetic.

This doesn't mean everything learned from rats and mice is completely irrelevant, only that most of it is.

If you understand this you'll be less likely to get excited when you see yet another highly touted article in the medical press about how diabetes has once again been cured in some lucky rodent--or perhaps not so lucky rodent, as they are "sacrificed" and dissected as part of the experiment.

Even if diabetes really were cured in a mouse with a transgenic human diabetes gene, your celebration should be muted. There are hundreds of unrelated gene defects that cause diabetes in humans.

And any study that suggests that one nutrient or diet cures diabetes in rodents and hence you should be eating it--well, I have enough respect for your intelligence not to have to spell out just how silly that is. Especially since rodents have evolved over many millions of years to live on high carb seed-based diets, unlike humans.


trinkwasser said...

The Sedge Warbler is a small transsaharan migrant bird. In order to make the journey they double their weight rapidly. They do this by eating insects - but what I didn't realise until recently is they eat high carb insects! Plum reed aphids are stuffed full of sugars from the plant sap they suck.
Smaller creatures are more affected by food shortages so it would make evolutionary sense that they would have genes which can switch them rapidly in and out of weight gain mode.
Our genes don't switch between modes nearly so quickly (or at all).
This may be one explanation as to why those damn "diabetic mice" can be "cured" so easily, and we can't.
Cows, and even Tilapia, appear to get dyslipidemia from the feeding of excess grains (not to mention geese and fatty liver) so there are probably similarities in the biochemistry of the process somewhere down the line which are worth studying, there may well turn out to be *some* common genes but I suspect more differences than similarities between species especially taking size into account.
Diabetic elephants may be worth studying but take a long time to breed and are hard to fit into a lab, probably two reasons they concentrate on rats and mice.

David Yolleck said...

What about our Type I research friend, the nonobese diabetic mouse?


Jenny said...


I do not know enough about the NOD mouse to comment intelligently, but since humans with "type 1" diabetes have various different genetic make ups it is not likely that the mouse model is all that close to the various human causes for autoimmune diabetes.

But mice have very different physiologies, pancreases etc, from humans. That is why none of the mouse diabetes "cures" so far has done anything for people.