Without insulin replacement, DM1 mice exhibit chronic, persistent hyperglycemia, glycosuria and fail to gain weight. In contrast, thanks to Banting and Best, very few human type 1 (or 2) diabetics go without insulin today. Rather, improper dosing or timing of insulin injections leads to drastic variations in glucose levels, biased towards insulin-induced hypoglycemia followed by compensatory food intake and weight gain. Specifically - is insulin replacement in DM1 STZ mice necessary to draw meaningful conclusions about the human disease?
Ya, there is no complications in using the same model, because the secondary complications are well produced by that models.
This is a very interesting topic. I have studied TGF-beta in mouse diabetic nephropathy many years ago, in rats with STZ induced hyperglycemia. We found TGF-beta began to be distributed in mesangium and glomerular structures after 16 weeks from the start of hyperglycemia. Many years later, TGF-beta came to be identified in human diabetic nephropathy, and today it is well defined that it is a major regulator of extra-cellular matrix prodution in mesangium, the principal finding in human diabetic nephropathy. We found that Wistar rats with STZ induced diabetes was a good model for diabetic nephropathy.
Well Insulin therapy in mice do prevent a lot of cardiac complications and I have studied it in a genetic model but not in STZ. Here is a paper for your perusal to find out the best models to study diabetic nephropathy.
Impact of genetic background on nephropathy in diabetic mice
Susan B. Gurley,1
Submitted 17 May 2005; accepted in final form 9 August 2005
I found rescue in diastolic function after insulin treatment in a model of Type 1 diabetic cardiomyopathy.
Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function.
Basu R
The STZ model is widely used and has a benefit of temporal induction of diabetes but there are reports of STZ toxicity and its effects on the heart. Genetic models are devoid of this complications.
Alloxan induced model is not long lasting so not much useful for development of complications. the animal may recover from hyperglycemia within one month before development of complications
We use an STZ model of murine diabetes and have found that insulin can be required for the mice to survive to the study endpoint. To avoid the improper dosing and timing of insulin that can lead to the dramatic changes in blood glucose you mentioned, we use a subcutaneous insulin pellet that slowly releases insulin overtime. We also use strict criteria of when the mice can receive a pellet to avoid any risk of hypoglycemia. However I have found that in mice with on a different genetic background from our typical model there may be great resistance to STZ induced diabetes and therefore no need for insulin supplementation.
I had exposure on Multiple STZ induced type-1 diabetes. It had shown less mortality and animal had survived more than 5 weeks after induction and sustained 4 weeks of treatment. in the insulin treated group there is a significant body weight increase but it had not shown any significant triglyceride increase in comparision with disease control. Why?
Sandeep I may be misreading your question. Why would you expect triglycerides (TG) to rise in insulin treated mice? My understanding was that insulin reduced TG and thus higher TG levels would be expected in mice with poorly controlled diabetes. Is the significant body weight increase due to fat (where you would expect higher TG) or lean mass? Poorly controlled type 1 can lead to muscle atrophy phenotype which could explain the weight difference between the groups. And if the mice were heavier due to more muscle mass there would not be a rise in TG.
Thank you sir.......... There is a significant increase in the body weight of insulin treated group at 5 IU/kg dose.
You may use this model for diabetic complications, but you have to control blood glucose and extend survival time of animal by giving then insulin 1 or 2 unit/kg/week. For diabetic cardiomyopathy you can check Serum CK and LDH, for nephropathy Creatinine clearance rate and albumin clearance can be check time to time to conform the status of diabetic complications.
STZ induced diabetes in mouse or rat is not a good model to study natural history of diabetes. We used this model to study the effect of hyperglycemia in spontaneously hypertensive rats. Many rats became sick due to extremely high glucose and died despite treatment with insulin. This is the citation of the work: Susic D, Mandal AK, Javovic D, Radujkovic G, Keutea D: Streptozotocin-induced diabetes lowers blood pressure in spontaneously hypertensive rets. Clin Exp Hypertens: Theory and Practice 1990; A12: 1021-1035
Drug-induced diabetes in rats is a good model to study diabetic complication of diabetes.
http://www.nature.com/articles/srep21752
Yes, STZ is better than Alloxan in inducing Diabetes in rats. Alloxan is more mortal and has toxic effects on islets of Langerhans, it also affects other organs, produces severe uncontrollable diabetes and causes a high loss in body weight. Also, you'll need higher doses to get the same diabetic effect by using lower doses of Streptozotocin which is more specific and less harmful.
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