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THE INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC)

IACUC / LARC STANDARD PROCEDURES

Diabetes Induction (Posted May 2008)

Description of procedure:

Induction of Chemically Induced Diabetes:

  1. Inject mice (aged 6 weeks or older) i.v. or i.p. with alloxan (70-90 mg/kg) or i.p. with streptozotocin (STZ) (200-400 mg/kg).
  2. Beginning on the day after the alloxan or STZ injection, blood sugar levels of each mouse are checked daily or every other day for 5-7 days by following the Blood Glucose Monitoring SOP.
  3. Two to five days after the development of diabetes (indicated by a blood glucose level of >150 mg/dL) mice receive an insulin-secreting pellet if they are required for further long-term study. 
  4. Monitor mice weekly once insulin pellets are implanted. (Pellets are implanted subcutaneously—see Standard Procedure for Implantation of insulin-secreting pellet)

Maintenance of Chemically induced Diabetes:

  1. Insulin pellets, releasing approximately 0.1 U /24 hr for >30 days, are implanted subcutaneously for a maintenance dose.  Mice weighing less than 25 grams only require one insulin pellet; larger mice whose blood glucose is not controlled within a normal range (70-150 mg/dL) will receive two insulin pellets.
  2. Evaluate mice for general appearance, ability to move normally around cage and reach food and water, ability to eat and drink, grooming habits, skin color, lethargy, aggression (animals will be housed individually if aggressive behavior is shown). Evaluate mice using the Body Condition scoring index.  Mice will be evaluated daily for the first 5 days after treatment with alloxan or STZ, and weekly thereafter.
  3. Mice with Body Condition score ≤2 will be euthanized. Mice with a glucose level of >400 mg/dL will be euthanized.

NOTE: More frequent cage changes or alternate bedding or method of housing may be required.

Literature search words required:

Literature search was performed for refinement of this Standard Procedure on August 21, 2007

Key Words

Search Site

Years Covered

Diabetes, alloxan, streptozotocin, mice

Pubmed

1958-May 2008

Diabetes AND streptozotocin AND mice

Altweb

Full database up to May 2008

Agents:

STZ, alloxan, insulin

All agents administered to animals should be listed in the “Agents” section of RIO.  This procedure requires anesthetics (for implantation of insulin pellet).

Adverse Effects:

Adverse Effects

Procedure, Agent or Phenotype

Potential Adverse Effects

Management

Uncontrolled diabetes

Weight loss, hypoglycemia, dehydration

Euthanasia

 

Monitoring Parameters

Monitoring Parameters

Frequency

PI/Lab will Document

General appearance/activity

First 5 days after alloxan & STZ & 1-2x’s/week thereafter

No

Ability to move around cage/eat & drink

First 5 days after alloxan and STZ & 1-2x’s/week thereafter

No

Blood glucose

1-7x’s/week & weekly after placement of implant

Yes

Body condition scoring

First 5 days after alloxan and STZ & 1-2x’s/week thereafter

Yes

 

Describe the conditions, complications, and criteria (e.g. uncontrolled infection, loss of more than 15% body weight, etc.) that would lead to removal of an animal from the study, and describe how this will be accomplished (e.g. stopping treatment, euthanasia).

Mice with Body Condition score ≤2 will be euthanized. Mice with a glucose level of >400 mg/dL will be euthanized. 

 

For all investigators housing animals with tumor formation, skin lesions, neurological deficits, or that are in Category E, list the expected characteristics/clinical presentations and endpoints of the animal model and the criteria for euthanasia. Note: The IACUC also requires such lists to be posted in the respective animal rooms and monitored by the IACUC compliance staff and LARC, to assure PI adherence to the endpoints listed.