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Zucker diabetic fatty (ZDF) rats_Type II diabetes

Model advantages

The Zucker Diabetic Fatty (ZDF) rat fed a lipid-rich diet, closely mimics human adult onset of type II diabetes and its related complications. In time, ZDF rats evolve from a model of metabolic syndrome to a type II diabetic rat based on impaired glucose tolerance caused by the inherited obesity gene mutation which leads to insulin resistance.


Pathophysiological features

Metabolic features

  • Age-dependent evolution from insulin resistance to type II Diabetes mellitus (figure 1)
  • Variable hyperinsulinemia
  • Hyperglycemia
  • Hypertriglyceridemia / Hypercholesterolemia
Figure 1: Age-dependent evolution of glucose metabolism in ZDF rats.
Figure 1: Age-dependent evolution of glucose metabolism in ZDF rats.

Cardiovascular features

  • Vascular endothelial dysfunction (aorta, superior mesenteric artery, ) from 20 weeks of age (figure 2)
Figure 2: Comparison of endothelium-dependent relaxations in ZDF and in their control (Lean) obtained in in vitro experiments performed in aortic and superior mesenteric artery rings. (2-way ANOVA, ***P<0.001) (Pelvipharm, internal data).
Figure 2: Comparison of endothelium-dependent relaxations in ZDF and in their control (Lean) obtained in in vitro experiments performed in aortic and superior mesenteric artery rings. (2-way ANOVA, ***P<0.001) (Pelvipharm, internal data).

Other pathophysiological features

  • Nephropathy
  • Neuropathy
  • Blindness
  • Impaired wound healing

Summarized methodology

  • ZDF: homozygous for non-functional leptin receptors (ZDF/Gmi fa/fa)
  • Lean controls: homozygous for normal receptors remain lean and normoglycaemic
    (ZDF/Gmi +/?)
Related Pelvipharm bibliography
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