Commentary Cell Science Reviews Vol 6 No 1 ISSN 1742-8130

Metformin for diabetes? New tricks of old drugs

It is widely accepted that metformin suppresses hepatic glucose production but its mechanism of action has previously remained elusive. A recent paper in Cell has however demonstrated that both insulin and metformin phosphorylate the transcriptional coactivator CREB binding protein (CBP) at serine 436. This process is mediated via atypical Protein Kinase C (aPKCι/λ), resulting in dissociation of the CREB-CBP-TORC2 transcription complex and subsequent reduction in gluconeogenic enzyme gene expression The authors further demonstrated that in obese, hyperglycaemic mice with insulin resistance, metformin, but not insulin, is able to stimulate hepatic CBP phosphorylation by bypassing the block in insulin signalling. They suggest that recognition of the critical action of CBP phosphorylation at serine436 by metformin may lead to therapeutic advances.

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