A new player involved in the regulation of metabolism, fat accumulation and liver cancer is reported in Nature Communications this week. This finding may have important implications for the use of specific insulin-sensitizing drugs for the treatment of type-2 diabetes. PTEN is an important protein in the signalling pathway that regulates glycolysis - the process by which glucose and other sugars are broken down to generate energy. Mutations in PTEN are known to cause liver enlargement, fat accumulation and eventually liver cancer in mice. Pende and colleagues show that mice with PTEN mutations have an abnormally active protein called PPARγ, which is responsible for increasing the expression of two key enzymes of glycolysis, with roles in liver cancer. They also show that activation of PPARγ causes massive proliferation of liver cells and fat accumulation. Given that PTEN is one of the most frequently mutated genes in cancer, these findings have important implications for the use of drugs that activate PPARγ as a strategy for diabetes treatment.
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