Hellos.
Im seeking advice on what would be the best model of T2D in rats given the following constraints:
1) I do not prefer leptin or leptin receptor deficient models since these mutations rarely occur in humans
2) I do not prefer the high fat diet plus low dose STZ model because I want to avoid possible off-targets effesct of STZ (we are looking at the pancreas metabolome)
3) The Wistar and Swiss Webster rats fed a high fat diet seem promising, but its not clear how much insulin resistance and ß-cell loss these rats develop, which are our main interests. Are these models of early stage T2D?
Are there other good advanced-stage models?
Thank you
I used leptin/ghrelin receptor defunct models as well as STZ-induced ones. You can use alloxan (40-200 mg/kg/rat) instead of STZ
If you do not want to induce T2D chemically in your rats, use ob/ob (obese) models or KK mice, corpulent (cp) rats or frequently used Zucker fatty rats (ZFRs). However, here are some other models you can use including obese, non-obese, diet and surgically-induced T2D rats or mice.
Non-obese models such as:
1. Cohen diabetic rat
2. Torri rat
3. non-obese mutant C57 BL/6 (Akita) mouse
4. Goto-Kakizaki rat
5. ALS/Lt mouse
Furthermore, sand rats and Acomys calirinus (spiny mouse) have inherently low insulin secretors.
I would suggest the Goto-Kakizakii rat from Taconic for your specific purposes. Here is a good comparison between the Goto-Kakizaki and high fat diet models of T2DM.
Article Goto-kakizaki Rats: Its Suitability as Non-obese Diabetic An...
Hi David,
This is not a simple nor a straightforward question to answer. Simply because, the clinical diagnosis referred to as DMT2 is not of a single nature. As there is no animal model replicates the actual human disease. All what we can do is mimic some group of symptoms manifestation characteristic to this pathology at certain stage or age.
I would start by filtering the question to: What? (the pathophysiologic basis for drug development and therapy? the beta cells dysfunction at the molecular level? The insulin dynamics in relation to metabolic paradigm, etc … Where? ( in the whole body or in certain organs) and, When? ( which you are referring to in your question as “advanced-stage” does it mean longstanding duration of the pathology , or the early/late age onset ?). To better understand how different rodent models of DMT2 (genetic, diet or chemically induced ) can serve you "Best” in your quest as a standardized, reproducible and translational representative of DMT2, I would recommend an authoritative and evidence-based reviews that will help you formulate an idea how each model works, their strengths and weaknesses.
Personally, I have been working with GK rats and, diet induced metabolic syndrome in SD rats. Each of which represents only certain aspects of the human condition.
wish you all the best in your research.
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