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Metformin inhibits glycogen synthesis and gluconeogenesis in cultured rat hepatocytes
Author(s) -
Otto M.,
Breinholt J.,
Westergaard N.
Publication year - 2003
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1046/j.1463-1326.2003.00263.x
Subject(s) - glycogenolysis , gluconeogenesis , glycogenesis , glycogen , metformin , medicine , glycogen phosphorylase , endocrinology , glycogen synthase , glycolysis , chemistry , biology , metabolism , insulin
Aim: Glycogen synthesis, and glucose and lactate production were examined in cultured rat hepatocytes preincubated with metformin (0–500 µ m ) for 24 h. Methods: Cells incubated with[1‐ 13 C]‐glucose and [1‐ 13 C]‐lactate allowed us to study the effect of metformin on glucose production from glycogenolysis and gluconeogenesis in a detailed manner using NMR spectroscopy. 1 H and 13 C‐filtered 1 H‐NMR spectra were recorded by using flow‐injection technique. Results: Metformin decreased glycogen synthesis in a dose‐dependent manner with an IC 50 value of 196.5 µ m . This effect could not be reversed by the presence of the glycogen phosphorylase inhibitor DAB, suggesting that glycogenolysis was not affected. A clear correlation between glucose production and glycogen content (0.97 < R < 0.99; p < 0.001) and lactate production and glycogen content (0.97 < R < 0.99; p < 0.001) was observed. Moreover, a strong inhibition (62%, p < 0.001) of glucose produced from lactate/pyruvate (3 m m /0.3 m m ) was observed in cells treated with 350 µ m metformin. Conclusion: Hepatocytes preincubated for 24 h in the presence of metformin at clinically relevant concentrations showed impaired glycogenesis as well as gluconeogenesis.