Streptozotocin‐Induced Diabetic Models in Mice and Rats

Brian L. Furman1

1 Strathclyde Institute of Pharmacy & Biomedical Sciences, Glasgow, Scotland
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.47
DOI:  10.1002/0471141755.ph0547s70
Online Posting Date:  September, 2015
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Abstract

Streptozotocin (STZ) is an antibiotic that produces pancreatic islet β‐cell destruction and is widely used experimentally to produce a model of type 1 diabetes mellitus (T1DM). Detailed in this unit are protocols for producing STZ‐induced insulin deficiency and hyperglycemia in mice and rats. Also described are protocols for creating animal models for type 2 diabetes using STZ. These animals are employed for assessing the pathological consequences of diabetes and for screening potential therapies for the treatment of this condition. © 2015 by John Wiley & Sons, Inc.

Keywords: streptozotocin; type 1 diabetes mellitus; hyperglycemia; insulin deficiency; insulin resistance; insulitis; mouse or rat; nicotinamide; high‐fat; type 2 diabetes mellitus

     
 
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Table of Contents

  • Introduction
  • Basic Protocol 1: Induction of Type 1 Diabetes Mellitus in Mice Using Repeated Low Doses of Streptozotocin
  • Alternate Protocol 1: Induction of Type 1 Diabetes Mellitus in Mice Using a Single, High Dose of Streptozotocin
  • Basic Protocol 2: Streptozotocin‐Induced Type 1 Diabetes Mellitus in Rats
  • Basic Protocol 3: The Streptozotocin‐Nicotinamide Rat Model
  • Basic Protocol 4: The Fat‐Fed Streptozotocin Rat Model
  • Commentary
  • Figures
     
 
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Materials

Basic Protocol 1: Induction of Type 1 Diabetes Mellitus in Mice Using Repeated Low Doses of Streptozotocin

  Materials
  • C57BL/6 or CD‐1 male mice: 25 g, 8 to 12 weeks old (Jackson Laboratory or Taconic); 12 to 20 animals per treatment group are recommended; Balb/cJ mice are resistant to the induction of diabetes using this treatment regimen (see Zunino et al., ).
  • Standard rodent chow diet (Harlan)
  • 50 mM sodium citrate buffer (enzyme grade; Fisher), pH 4.5: prepared immediately before use
  • Streptozotocin (STZ; Sigma)
  • 10% (w/v) sucrose (Sigma): prepared just before use
  • Test compound(s)
  • Rodent cages
  • Temperature‐, humidity‐, and light‐controlled housing
  • 1.5‐ml microcentrifuge tubes
  • Aluminum foil
  • 1‐ml syringes
  • 25‐G needles
  • One Touch Basic blood glucose monitoring system (Lifescan)
  • Additional reagents and equipment for injection of mice (Donovan and Brown, ) and blood collection from mice (Donovan and Brown, )

Alternate Protocol 1: Induction of Type 1 Diabetes Mellitus in Mice Using a Single, High Dose of Streptozotocin

  Materials
  • Sprague‐Dawley or Wistar male rats: 150 to 200 g, 8 to 10 weeks old (Charles River Breeding Laboratories); 10 to 16 per treatment group recommended
  • Standard rodent chow diet (Harlan)
  • 50 mM sodium citrate buffer (enzyme grade; Fisher), pH 4.5: prepared just before use
  • Streptozotocin (STZ; Sigma)
  • 10% (w/v) sucrose (Sigma): prepared just before use
  • Test compound(s)
  • Rodent cages
  • Temperature‐, humidity‐, and light‐controlled housing
  • 1.5‐ml microcentrifuge tubes
  • Aluminum foil
  • 1‐ml syringes
  • 23‐G needles
  • One Touch Basic blood glucose monitoring system (Lifescan)
  • Additional reagents and equipment for injection of rats (Donovan and Brown, ), blood collection from rats (Donovan and Brown, ), and anesthesia of rats (Donovan and Brown, )

Basic Protocol 2: Streptozotocin‐Induced Type 1 Diabetes Mellitus in Rats

  Materials
  • Sprague‐Dawley or Wistar male rats: 150 to 200 g, 8 to 10 weeks old (Charles River Breeding Laboratories); 10 to 16 per treatment group, recommended
  • Standard rodent chow diet (Harlan)
  • Nicotinamide (Sigma)
  • 0.9% (w/v) sodium chloride
  • 50 mM sodium citrate buffer (enzyme grade; Fisher), pH 4.5: prepared immediately before use
  • Streptozotocin (STZ; Sigma)
  • Test compound(s)
  • Rodent cages
  • Temperature‐, humidity‐, and light‐controlled housing
  • 1‐ml syringes
  • 23‐ and 25‐G needles
  • One Touch Basic blood glucose monitoring system (Lifescan)
  • Additional reagents and equipment for injection of rats (Donovan and Brown, ), blood collection from rats (Donovan and Brown, ), and anesthesia of rats (Donovan and Brown, )

Basic Protocol 3: The Streptozotocin‐Nicotinamide Rat Model

  Materials
  • Sprague‐Dawley or Wistar male rats: 150 to 200 g, 8 to 10 weeks old (Charles River Breeding Laboratories), 10 to 16 per treatment group
  • A high‐fat diet: 60% fat by caloric content (D12492 diet; Research Diets, http://www.researchdiets.com/opensource‐diets/diet‐induced‐disease‐models/obesity)
  • A low‐fat diet from the same supplier for control animals (with the only difference between the diets being the % of the caloric intake provided by fat)
  • 50 mM sodium citrate buffer (enzyme grade; Fisher), pH 4.5: prepared immediately before use
  • Streptozotocin (STZ; Sigma)
  • Test compound(s)
  • Rodent cages
  • Temperature‐, humidity‐, and light‐controlled housing
  • 1‐ml syringes
  • 23‐G needles
  • One Touch Basic blood glucose monitoring system (Lifescan)
  • Additional reagents and equipment for injection of mice (Donovan and Brown, ) and blood collection from mice (Donovan and Brown, )
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Figures

Videos

Literature Cited

Literature Cited
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Internet Resources
  http://www.AMDCC.org
  Web site for Animal Models of Diabetic Complications Consortium (AMDCC), providing new animal models of diabetic complications, with the goal of identifying the most appropriate animal models to study the etiology, prevention, and treatment of diabetic complications.
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