Cology

• GK rat


  • Develops features that can be compared with the complications of diabetes seen in humans
• Complications of diabetes in GK rats

  • Renal lesions (Nephropathy)
  • Symptoms similar to humans
  • Structural changes in peripheral nerves (Neuropathy)
  • Abnormalities of the retina (Retinopathy)
• Animals have provided significant contributions to modern medical understanding and advancement
• Novel surgical techniques developed using animals

  • Tracheostomy, initially performed by Ibn Zuhr on goats in the 12th century
  • Laparoscopy, which originated from Georg Kellings' work using dogs in the 1900s
• Animal experiments have contributed significantly to the development of vaccines, antibiotics, and our fundamental understanding of human disease processes
• Approximately 20 million animal subjects are used in biomedical research, dominated by mouse and rat models
• The use of animals in research has been called into question by the scientific community due to concerns about their clinical validity and application, as well as ethical concerns
• Advantages of Animal Models

  • Feasibility
  • Similarities to Human
  • Drug Safety
• Issues with Animal Models

  • Disparate animal species and strains, with a variety of metabolic pathways and drug metabolites
  • Different models for inducing illness or injury with varying similarity to the human condition
  • Variations in drug dosing schedules and regimen that are of uncertain relevance to the human condition
  • Variability in the way animals are selected for study methods of randomization, choice of comparison therapy (none, placebo, vehicle), and reporting of loss to follow up
  • Small experimental groups with inadequate power, simplistic statistical analysis that does not account for potential confounding, and failure to follow intention to treat principles
  • Nuances in laboratory technique that may influence results may be neither recognized nor reported—eg methods for blinding investigators
  • Selection of a variety of outcome measures, which may be disease surrogates or precursors and which are of uncertain relevance to the human clinical condition
  • Length of follow up before determination of disease outcome varies and may not correspond to disease latency in humans
• The Animal Welfare Act, passed in the United States in 1970, stipulates that all experiments using animals provide adequate veterinary care, including the appropriate use of anesthetic, analgesic or tranquilizing drugs
• The three Rs


  • Replacement
  • Reduction
  • Refinement
• Creating Animal Models


  1. Surgery

  2. Pharmacological inhibition

  3. Genetics
• The Goto Kakizaki (GK) rat

  • The GK rat was developed by the selective breeding of Wistar rats with the highest blood glucose over many generations
  • The rats develop relatively stable hyperglycaemia in adult life
  • The fasting blood glucose is only mildly elevated but rises further on challenge with glucose
  • Both insulin resistance and impaired insulin secretion are present
• The GK rat


  • Develops some features that can be compared with the complications of diabetes seen in humans, including renal lesions, structural changes in peripheral nerves, and abnormalities of the retina