Metformin-associated lactic acidosis is not necessarily due to metformin accumulation; true type B (aerobic) lactic acidosis, i.e., without an apparent associated hypoxic factor, seems exceptional. Neither the severity of the clinical picture nor the degree of metformin accumulation predicted survival; rather, the prognosis was dependent upon the severity of the associated pathological conditions.

Aquaglyceroporin-9 (AQP9) facilitates diffusion of water and energy substrates such as glycerol and monocarboxylates. AQP9 is present in plasma membrane and mitochondria of astrocytes and catecholaminergic neurons, suggesting that it plays a role in the energetic status of these cells. Using specific small interference RNA directed against AQP9 in astrocyte cultures, we showed that glycerol uptake is decreased which is associated with an increase in glucose uptake and oxidative metabolism. Our results not only confirm the presence of AQP9 in astrocytes but also suggest that changes in AQP9 expression alter glial energy metabolism.

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