Hi, we are going to establish a STZ diabetic model and we have multiple questions. We would like to study CVD complications of diabetes. We are going to use mice WT.
Do we should administer STZ drug in a single dose?
When the animal shows 300 mg/dL glucose during three days I've read that is considered diabetic. Then do we should administer insulin? We would like to keep the glucose level high. I'm worried if we administer insulin glucose level will decrease back to normal level and we won't have complications.
Do you check glucose extracting a drop from the tail? Do you use test trips and lancing device like the one used by diabetic human?
Do you think we can keep the diabetic mice for three months? or this is to ambitious?
Many thanks!!!!
Aida
The Streptozotocin-Induced Diabetic Nude Mouse Model: Differences between Animals from Different Sources
Melanie L Graham,* Jody L Janecek, Jessica A Kittredge, Bernhard J Hering, Henk-Jan Schuurman
Abstract
Diabetes is induced in mice by using streptozotocin (STZ), a compound that has a preferential toxicity toward pancreatic β cells. We evaluated nude male mice from various sources for their sensitivity to a single high dose (160 to 240 mg/kg) of STZ. Diabetes was induced in male mice (age: median, 12 wk; interquartile range, 11 to 14 wk; body weight, about 30 g) from Taconic Farms (TAC), Jackson Laboratories (JAX), and Charles River Laboratories (CRL). Mice were monitored for 30 d for adverse side effects, blood glucose, and insulin requirements. In CRL mice given 240 mg/kg STZ, more than 95% developed diabetes within 4 to 5 d, and loss of body weight was relatively low (mean, 0.4 g). In comparison, both TAC and JAX mice were more sensitive to STZ, as evidenced by faster development of diabetes (even at a lower STZ dose), greater need for insulin after STZ, greater body weight loss (mean: TAC, 3.5 g; JAX, 3.7 g), and greater mortality. We recommend conducting exploratory safety assessments when selecting a nude mouse source, with the aim of limiting morbidity and mortality to less than 10%.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155402/
The use of animal models in diabetes research
Aileen JF King
Abstract
Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is due to an autoimmune destruction of the insulin-producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non-obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock-out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417415/
Dear Ali,
thanks for the papers, I've been reading multiple papers about the STZ model, I will also read these two. Do you use that mice model? I was wondering to get here some personal recommendations and tricks that are generally not detailed in the papers. For example, complications, use of insulin/type of insulin, dose, method to determine the glucose...
Thanks!
Aida
Dear Aida,
In our case we used a rat model and we only administered STZ but not insulin. We obtained the blood from the tail of the animals and just performed the glucose curve with or without the GSPE product administration. I believe that the model is not a transient one because it causes a chemical destruction of pancreatic beta-cells. The extension in time of this destruction should be checked in your mice.
Speaking from a personal experience; in inducing diabetes in mice with the intent of keeping them for 3 months without treatment you would need a lot of care and lots of attention all through the period. There would be mortalities so you should prepare for this by inducing extra animals. After an overnight fast administer STZ at 60-70 mg/kg intraperitoneal injection. STZ should be dissolved in ice cold saline (please ensure the STZ is measured using a precision balance, because too much can be catastrophic and with lesser than optimal dose diabetes may fail to induce).A number of research articles hve reported the use of citrate buffer at a pH of 4.5 (Ihave used both, with better results with ice cold saline). After administering STZ it would be good to give the mice 0,2-0,5ml (10 ml/kg) of 20% glucose to prevent mortalities from hypoglycaemic shock, you may need to give this once or twice if animals refuse to feed after induction, also make sure there is plenty of water in their drinkers
Animals are considered diabetic when their blood glucose levels are > or equal to 190 mg/dl (10.56 mmol/l) and above the choice of the cut off is usualiy determined by the age of the animals and/or the severity of diabetes you intend to study, Although considering the rational of your study animals with a cut off between 190 and 300 mg/dl are more likely to survive for three months without treatment. You do not need to administer insulin if it is not one of the standards of treatment in your study. If you need any more information, please fell free to contact me. All the best in your research.
Dear Mayte Blay and Adejoke Yetunde Onaolapo,
many thanks for your comments, I'm sure your experience will be really useful for my experiment. I have another quick question. Have you ever used BALB/c mice for that model? I've been reading that immunodepressed mice work better but we don't have now permission to use them. Do you think BALB/c will work for type 1 diabetes? I'm worried because I've been reading some papers where they say the model C57BL/6 is adequate for type 2 diabetes, not type 1. What about BALB/c?
Thanks!!!!
Aida
If you are using a chemical method of induction like STZ you do not need immunocompromised animals BALB/c mice would do just fine. the question as to what type of diabetes is induced with STZ is the topic of many debates and controversies I usually just keep to the terminology STZ induced diabetes rather than any specific type. Although more researchers are of the opinion that single large dose of STZ causes type 1 diabetes.
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