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Updated: Sep 29, 2026

A Model of Chronic Nutrient Infusion in the Rat
Published on: August 14, 2013
Acute effects of pioglitazone on glucose metabolism in perfused rat liver
Y Nishimura1, Y Inoue, H Takeuchi
1Third Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Abstract:
Pioglitazone, a thiazolidinedone derivative, decreases insulin resistance and improves hyperglycemia in insulin-resistant obese and/or diabetic animals. However, the mechanisms by which hyperglycemia is improved are not well defined. We investigated the effects of pioglitazone on hepatic glucose metabolism using a perfused rat liver model. Perfusion with the buffer containing 1-10 microM pioglitazone for 20 min dose-dependently increased the hepatic fructose 2,6-bisphosphate content, a potent activator of 6-phosphofructo 1-kinase. The fructose 2,6-bisphosphate level after 20 min perfusion with 10 microM pioglitazone was 64.9 +/- 14.5 pmol/mg.protein, significantly higher than the control (48.3 +/- 10.9 pmol/mg.protein). When the liver from a starved for 48 h rat was perfused with the buffer containing 2 mM lactate but no glucose, glucose was generated from lactate via the gluconeogenic pathway and flowed into the effluent perfusate at a constant rate of 31 +/- 0.6 mumol/g.liver/h. The addition of 10 microM pioglitazone decreased the glucose output rate to 19.3 +/- 3.8 mumol/g.liver/h. Dose-dependent inhibition of glucose output by pioglitazone was observed in the 1-10 microM dose range. These results indicate that pioglitazone may not only stimulate glycolysis but also inhibit gluconeogenesis in the liver. These acute and insulin-independent effects on hepatic glucose metabolism may partly account for the diverse anti-diabetic effects of pioglitazone.
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