Insulin Resistant rat model

Muscle Adipose tissue Liver Pancreas Macrophage
First-in-class rat nutritional model combining obesity, insulin resistance and dyslipidemia

Key benefits

  • Provides a noteworthy competitive advantage for your lead/drug compound, in terms of insulin resistance, obesity, dyslipidemia, and hepatic steatosis.
  • Merges glucose and lipid disorders in a UNIQUE animal model, for robust differentiation of your compound's efficacy and unwanted effects.
  • Tailor-made nutritional model obtainable in 5 to 8 weeks, depending on your scientific needs.
  • Palatable diet leading to rapid weight gain to detect a statistically significant impact of your compound on body weight/food intake.

Animal Model

  • Background Strain: Sprague Dawley (SD)
  • Gender/Weight/Age: Male rats, 240-260g, 7-8 weeks old
  • Diet: the RD diet®
  • Time on diet: 5-8 weeks
  • Positive reference compounds: rosiglitazone

 

Pathophysiological features

  • Obesity (mainly visceral)
  • Glucose intolerance
  • Hyperinsulinemia
  • Insulin resistance (hepatic and peripheral)
  • Mild dyslipidemia
  • Lipid intolerance
  • Impairment of FFA metabolism
  • Hepatic steatosis
  • Accumulation of triglycerides in tissues (liver and muscle)

Scientific and pharmacological relevance

  • Treatment: Rosiglitazone (once a day)
  • Duration: 15 days
  • Dose: 10 mg/kg
  • Normalization of fasting plasma glucose and insulin
  • Partial reduction in insulin resistance
  • Slight reduction in plasma FFA and TG
  • Reduction in FFA turnover, due to slower plasma FFA appearance

Characterization of the RD diet®

Insulin Reststant Rat graph 1

Body weight variations of rats fed chow (control), standard high-fat diet, and RD diet. 

Insulin Resistant rat graph 2
Insulin Resistant Rat graph 3

Euglycemic hyperinsulinemic two-step clamp with 3H-glc
in chow controls and RD diet-fed rats.

Insulin Resistant Rat graph 4

Liver weight and TG content in liver and muscle in control chow rats
and RD diet-fed rats.

Pharmacological validation of the RD dietŪ

Insulin Resistant Rat graph 5

Euglycemic hyperinsulinemic clamp in control chow rats and
RD diet-fed rats +/- rosiglitazone.

Insulin Resistant Rat graph 6
Insulin Resistant Rat graph 7

 
Whole-body FFA turnover in basal conditions in control chow rats and
RD diet-fed rats +/- rosiglitazone.

References and publications

Issandou M, Bouillot A, Brusq JM, Forest MC, Grillot D, Guillard R, Martin S, Michiels C, Sulpice T, Daugan A.
Pharmacological inhibition of Stearoyl-CoA Desaturase 1 improves insulin sensitivity in insulin-resistant rat models.
Eur J Pharmacol. 2009 Sep 15;618(1-3):28-36

Print Top
legend