Suppression of hepatic gluconeogenesis in long-term Troglitazone treated diabetic KK and C57BL/KsJ-db/db mice

Metabolism. 1995 Apr;44(4):486-90. doi: 10.1016/0026-0495(95)90056-x.


The orally effective antidiabetic agent Troglitazone (CS-045) exerts hypoglycemic effects in various insulin-resistant obese and/or diabetic animals. Since increased hepatic gluconeogenesis is a major cause of hyperglycemia in these diabetic animals, we evaluated the effect of long-term Troglitazone treatment on hepatic gluconeogenesis. Troglitazone was administered for 7 days to normal ddY mice, diabetic KK mice, diabetic C57BL/KsJ-db/db mice, and its heterozygote, db/+ mice, as a 0.1% or 0.2% food admixture. Troglitazone significantly decreased plasma glucose in diabetic KK and db/db mice, but not in normal ddY and db/+ mice. 14C incorporation into blood glucose from NaH14CO3 was measured to assess hepatic gluconeogenesis in diabetic KK and normal ddY mice. Hepatic gluconeogenesis was significantly increased in diabetic KK mice (P < .01) as compared with normal mice, and was significantly suppressed (P < .05) after 7 days of Troglitazone treatment (approximately 200 mg/kg/d). Glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) were significantly decreased but fructose-1,6-bisphosphate (FBP) was not significantly increased in the liver of diabetic db/db mice treated with Troglitazone for 7 days (approximately 80 mg/kg/d) as compared with control db/db mice. These changes in G6P, F6P, and FBP corresponded with the activity of fructose-1,6-bisphosphatase (Fru-1,6P2ase) and 6-phosphofructo-1-kinase (6-PF-1K), which determined the content of F6P and FBP. Namely, Fru-1,6P2ase was significantly decreased in Troglitazone-treated db/db mice as compared with control mice, whereas 6-PF-1K activity was not affected by Troglitazone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Animals
  • Chromans / pharmacology*
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism*
  • Fructose-Bisphosphatase / metabolism
  • Fructosediphosphates / metabolism
  • Gluconeogenesis / drug effects*
  • Glycolysis
  • Hypoglycemic Agents / pharmacology
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Phosphofructokinase-1 / metabolism
  • Reference Values
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Time Factors
  • Troglitazone


  • Chromans
  • Fructosediphosphates
  • Hypoglycemic Agents
  • Thiazoles
  • Thiazolidinediones
  • fructose 2,6-diphosphate
  • Phosphofructokinase-1
  • Fructose-Bisphosphatase
  • Troglitazone