DBM mice as a pharmacological model of maturity onset diabetes. Studies with metformin

Arch Int Pharmacodyn Ther. 1979 Sep;241(1):165-76.

Abstract

Hyperglycemic obese and hyperinsulinemic mice of DBM strain develop a diabetic syndrome which can be compared to human maturity onset diabetes. In this study 6 to 49 weeks old female mice were used. Hyperglycemia and concomitant obesity were observed at 9 weeks. Plasma immunoreactive insulin (IRI) was maximum at 15--20 weeks, then decreased progressively with broad individual variations. Metformin, administered at 200 mg/kg per os, ineffective dosage in normal mice, showed a strong hypoglycemic effect in younger mice (11--18 weeks) with a plasma IRI decrease and no blood lactate and liver glycogen alteration. Plasma metformin concentration curve showed an exponential elimination fitted to a one compartment model with a plasma half-life of 2.7 hours. Metformin-induced hypoglycemia was lower in older mice (23--29 weeks) and corroborated their lower initial plasma IRI. All these results are in accordance with those reported in man and show that DBM mice provide a suitable model for a better understanding of antidiabetic drugs effects.

MeSH terms

  • Aging
  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus / physiopathology
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / genetics*
  • Disease Models, Animal*
  • Female
  • Insulin / blood
  • Lactates / blood
  • Liver Glycogen / metabolism
  • Metformin / therapeutic use*
  • Mice
  • Mice, Inbred C57BL / metabolism*
  • Obesity

Substances

  • Blood Glucose
  • Insulin
  • Lactates
  • Liver Glycogen
  • Metformin