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Effect of STZ on Albino Wistar Rats

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jwilkineinstein

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Dear Sir/Madam,
My name is John and i been doing animal models for quite some time. Recently taken up Animal models in diabetic condition as the main topic. I had fixed several doses for inducing diabetes by STZ,50,55 and 60mg/kg.b.wt.As usual the animals were fasted overnight and STZ was prepared freshly along with normal saline. The chemical was than administered as ip .Blood glucose levels were raised up to 500mg/dl in 55 and 60mg/kg.b.wt but at 50mg/kg.b.wt the initial blood glucose levels were up to 150-200mg/dl,after the 7th day the blood glucose levels have come down to 65 and 70mg/dl.Iam confused.
I would request your good self to kindly help me in this regard and do the needful

.........................

Posted Dec 20, 2007, 12:26 PM
R Bishop

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jwilkineinstein,

Welcome to the fun world of making animals diabetic. Streptozotocin dosing in rats is typically done by two methods. At 55 and 65 you are in the "high" dose range. At this level you rapidly induce the killing of beta islets and you get very high glucose levels rapidly. The rats probably succomb soon after reaching 500mg/dl? At 50 mg/kg you are in the "low dose" range of this drug. You get an initial glucose rise response, then the animals can recover. this may be due to islet expansion and making more insulin which halts the drugs killing of beta cells though there is some argument about this. In mice we typically dose the animals on 5 consecutive days with 50mg/kg. Then we wait 4 weeks for an effect on blood glucose, after 8 weeks the glucose will reach 500 mg/dl as the beta cells are killed by immune mediated attack. You can get more info on this at the AMDCC.

http://www.amdcc.org/

Rb

.........................
"To those who would tear the world down: We will defeat you. To those who seek peace and security: We support you. And to all those who have wondered if America's beacon still burns as bright: Tonight, we proved once more that the true strength of our nation comes not from the might of our arms or the scale of our wealth, but from the enduring power of our ideals: democracy, liberty, opportunity and unyielding hope." -- Barack Obama, Nov. 4, 2008

Posted Dec 20, 2007, 18:23 PM
jwilkineinstein

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R Bishop said:
jwilkineinstein,

Welcome to the fun world of making animals diabetic. Streptozotocin dosing in rats is typically done by two methods. At 55 and 65 you are in the "high" dose range. At this level you rapidly induce the killing of beta islets and you get very high glucose levels rapidly. The rats probably succomb soon after reaching 500mg/dl? At 50 mg/kg you are in the "low dose" range of this drug. You get an initial glucose rise response, then the animals can recover. this may be due to islet expansion and making more insulin which halts the drugs killing of beta cells though there is some argument about this. In mice we typically dose the animals on 5 consecutive days with 50mg/kg. Then we wait 4 weeks for an effect on blood glucose, after 8 weeks the glucose will reach 500 mg/dl as the beta cells are killed by immune mediated attack. You can get more info on this at the AMDCC.

http://www.amdcc.org/

Rb

.........................

Posted Dec 24, 2007, 8:14 AM
jwilkineinstein

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Dear Sir,
Thanks a lot for your advice.I would like to bring to your kind attention that iam not a ADCC member,but i would be happy if iam one among the members and will do the needeful to the group.How do i go about?

Do you have any information in regard to Effect of STZ on rats.
Kindly help.
Thanking you sir,
Warm regards,
Wilkin

.........................

Posted Dec 24, 2007, 8:20 AM
Tony Rook

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jwilkineinstein -

It looks like to become a AMDCC member you must be either

An AMDCC funded investigator

or

Associated with a member laboratory


For more information about registering at AMDCC link here!

.........................
Tony Rook

Posted Dec 26, 2007, 23:33 PM
R Bishop

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jwilkineinstein said:
Dear Sir,
Thanks a lot for your advice.I would like to bring to your kind attention that iam not a ADCC member,but i would be happy if iam one among the members and will do the needeful to the group.How do i go about?

Do you have any information in regard to Effect of STZ on rats.
Kindly help.
Thanking you sir,
Warm regards,
Wilkin


I seems STZ effects rats very different from mice. Many labs seem to use 50 mg/kg i.p. injection and detect hyperglycemia within 24hrs.

Example
Experimental Diabetic Model
Male Wistar rats (~300 g) received a single injection of STZ (50 mg/kg, dissolved in 0.01 M citrate buffer, pH 4.5) into the penile vein, after a fasting overnight for approximately 12 hours. An equivalent volume (0.1 mL) of vehicle (0.01 M citrate buffer, pH 4.5) was administered to control rats. Development of diabetes was confirmed 72 h later by the presence of hyperglycemia (> 350 mg/dL).

So my question is are you using saline or citrate pH 4.5 to inject the drug? I know that citrate seems critical to the drug performance. Also why are you needing to do dose curve for the drug? It seems your 55mg.kg dose works fine to induce diabetes?

Also I wasnt suggesting you join the AMDCC, only that their website has many excellent protocols.

Best


Rb

.........................
"To those who would tear the world down: We will defeat you. To those who seek peace and security: We support you. And to all those who have wondered if America's beacon still burns as bright: Tonight, we proved once more that the true strength of our nation comes not from the might of our arms or the scale of our wealth, but from the enduring power of our ideals: democracy, liberty, opportunity and unyielding hope." -- Barack Obama, Nov. 4, 2008

Posted Dec 27, 2007, 22:39 PM
Chintan Patel

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Dear John

Let me tell you the basic mechanism of action of SZT. As we all know it is a cytotoxic chemical which has direct effect on the beta cell. After the STZ injection it starts to destroy the beta cell and hence the insulin level will be effected therefore to neutralize that effect the secretion of insulin from remaining beta cell will be higher. That is why at one week you got the low level of glucose because the animals you are using might have more resistance then normal animals. So be cool and calm and wait for another one week, you will definitely get the hyperglycemic model. If you required then you can inject another dose of STZ at 2nd week after checking the glucose level.

As Rb has already asked you, if you have used normal saline then use 0.01 M citrate buffer. I think this will solve your problem. If not then let us know we will try to resolve it by discussing.

People are using STZ model mainly for Type I diabetes only

Chintan

.........................

Posted Jul 27, 2008, 21:04 PM
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