Metformin: The diabetes drug may actually make you smarter

Metformin is a drug that is a member of the biguanide class. It is currently the most widely prescribed insulin-sensitizing drug in current clinical use for the treatment of type 2 diabetes. For more information on metformin action in treating type 2 diabetes visit the Diabetes page on The Medical Biochemistry Page. Metformin administration does not lead to increased insulin release from the pancreas and as such the risk of hypoglycemia is minimal. The major site of action for metformin is the liver. A major mechanism for metformin action is the activation AMP kinase (AMPK: for more on AMPK function visit the AMPK page). Recent work has shown that AMPK activation in turn activates a class of protein kinase C (PKC) isoforms referred to as atypical PKC (aPKC), in particular aPKC iota and aPKC zeta. These two aPKC enzymes then can phosphorylate a transcriptional coactivator known as cAMP response element-binding protein (CREB)-binding protein (CBP). CBP has been shown to be necesasary for optimal differentiation of embryonic neural progenitors. Taken together it is suggestive that metformin might indeed activate aPKC in neural stem cells and allow their recruitment into the adult brain.

In a study published July 6, 2012 in Cell Stem Cell the ability of metformin to induce neurogenesis and enhance spatial memory formation was demonstrated. http://dx.doi.org/10.1016/j.stem.2012.03.016 The study showed that metformin did in fact activate aPKC iota and aPKC zeta and that this resulted in rodent and human neurogenesis in a cell culture system. Within the adult mouse CNS, metformin was also shown to activate neurogenesis in the hippocampus. This metformin-induced neurogenesis required the action of CBP and was measured via spatial learning tasks involving a water maze.

The take home from this study is that there may be a new and potentially powerful function for metformin in humans. The drug may be used for therapeutic intervention in treating the injured or degenerating nervous system.

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