Regulatory Effects of Metformin, an Antidiabetic Biguanide Drug, on the Metabolism of Primary Rat Adipocytes

Metformin is a biguanide compound commonly applied in humans with type 2 diabetes. The drug affects different tissues, including fat tissue. The direct influence of metformin on cells of fat tissue, i.e., adipocytes, is poorly elucidated. In the present study, the short-term (4-h) effects of metformin on lipogenesis, glucose transport, lipolysis, and lactate release in primary rat adipocytes were explored. It was demonstrated that metformin reduced insulin-induced lipogenesis and increased glucose transport into adipocytes. The tested compound also decreased lactate release from fat cells. It was shown that metformin substantially limited lipolysis stimulated by epinephrine (adrenergic receptor agonist) and dibutyryl-cAMP (direct activator of protein kinase A). Moreover, metformin decreased the lipolytic process triggered by DPCPX (adenosine A₁ receptor antagonist). In the case of each lipolytic stimulator, the drug evoked a similar inhibitory effect in the presence of 3 and 12 mM glucose. The lipolytic response of adipocytes to epinephrine was also found to be reduced by metformin when glucose was replaced by alanine. It was demonstrated that the tested compound limits the release of both glycerol and fatty acids from fat cells. The results of the present study provided evidence that metformin significantly affects the metabolism of primary rat adipocytes. Its action covers processes related to lipid accumulation and release and occurs after relatively short-term exposure.