Glycogen synthesis from dihydroxyacetone in isolated rat hepatocytes

Abstract

Glycogenolysis and gluconeogenesis are sensitive to nutritional state and their balances are disrupted in the liver by different pathological states. The regulation of the balance between glucose production and synthesis of glycogen continues to be a matter of investigation because of its implications in diseases and its value for therapeutics. We used the gluconeogenic precursor dihydroxyacetone (DHA) to study glycogen synthesis in isolated rat hepatocytes under gluconeogenic conditions. We used a glycogen phosphorylase (GP) inhibitor, 2-deoxy-2-fluoro-α-D-glucopyranosyl fluoride (F₂Glc) to prevented GP from breaking up glycogen into glucose subunits and had a pool of glucose in the medium. Therefore, we evaluated the contribution of DHA as a unique source of carbohydrates on glycogen metabolism. We showed that DHA increased G6P levels that induced both GS activation and its translocation and, thus, an increment of glycogen deposition in a similar way as glucose did.

Graphical Abstract

Keywords:

• Dihydroxyacetone
• gluconeogenesis
• glycogen phosphorylase
• glycogen synthase
• hepatocyte

Acknowledgments

We thank Dr. Joan J. Guinovart for sharing his laboratory equipment and the Department of Organic Chemistry of the University of Barcelona for providing 2-deoxy-2-fluoro-α-D-glucopyranosyl fluoride. We also thank Ms. Mary T. Bauer from ADLOM TRAINING SL for assistance in preparing the English manuscript.

Additional information

Funding

This work has been supported by a grant from the Ministry of Science and Technology (DGI-MCYT), Spain [BMC2002-00705].