METFORMIN is an effective treatment in the reduction of overactive glucose production associated with diabetes and other disorders related to insulin resistance.
It is also the most frequently prescribed drug for type 2 diabetes.
Despite its success, its exact mechanism of action has remained imperfectly understood.
At the Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, researchers lead by Dr Morris J. Birnbaum took a new look at the normal regulation of glucose.
It was known that without food intake, glucose levels decrease and the pancreas secretes glucagon to signal the liver to produce glucose.
While investigating the effect of Metformin on the glucagon cascade, the team identified a novel mechanism in animal models: Metformin antagonises the action of glucagon thus reducing fasting glucose levels.
The team showed that Metformin leads to an accumulation of adenosine monophosphate (AMP) which inhibits an enzyme called adenylate cyclase.
This reduces levels of cyclic adenosine monophosphate (cAMP) and protein kinase activity, eventually blocking glucagon-dependent glucose output from liver cells.
From this understanding, Birnbaum and his colleagues surmise that adenylate cyclase could potentially become a new drug target by-passing metformin’s effect on cell mitochondria and possibly limiting other adverse side-effects experienced by many people taking Metformin.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment.