Metformin-carbonic anhydrase interaction facilitate lactate accumulation in type 2 diabetes

Author(s): Ibrahim Salihu Ismail*

Metformin has emerged as the most widely prescribed antidiabetic medication for the management of type 2 diabetes. Among the widely accepted mode of its action, is reduction of hepatic glucose production. The risk of lactic acidosis is common with metformin usage. Recent data revealed that Metformin, in addition to its glucose reduction action, might be responsible for specifically inducing lactic acidosis. The present review can help us explore the possible mechanism by which this process occurs in order to develop means of avoiding lactic acidosis. Metformin exerts its action, by inhibiting hepatic gluconeogenesis. Carbonic anhydrase a ubiquitous Zinc metalloenzyme has been found to not only facilitate in/out flux of lactate through monocarboxylate transporters across cells, but also to be responsible for the provision of bicarbonate for the first step of hepatic gluconeogenesis. Thus inhibition of carbonic anhydrase will results in defective provision of bicarbonate for hepatic glucose production and hence low blood glucose. Metformin decreases hepatic lactate uptake, through yet to be fully explained mechanism, however, these effects require further investigation. Here, the role of carbonic anhydrase in lactate transport and the rise in blood lactate level upon carbonic anhydrase inhibition has been discussed. New understanding of the carbonic anhydrase inhibition action of metformin in the liver and the implications of carbonic anhydrase inhibition has been discussed and will be important in design and development of novel antidiabetic drugs. Google scholar database search was performed using the following terms: “metformin”, “gluconeogenesis”, “carbonic anhydrase”, “lactate”. There was no restriction on the year the paper was published. Only manuscripts written in English were considered.

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