Effect of metformin on global gene expression in liver of KKAy mice

Background: Metformin is a first-line drug for treating type 2 diabetes mellitus, yet its mechanism remains only partially understood and controversial. In this study we assessed a global gene expression profiling in liver of KKAy mice affected by metformin. This study aimed to identify the novel anti-diabetic mechanisms of metformin. Methods: After KKAy mice were administered metformin for 5 weeks, the gene changes profile in the livers of KKAy mice were assessed by using the Agilent whole mice genome oligo microarray. Results: Metformin altered the gene expression profiles in liver of KKAy mice. To our best knowledge, some genes have not been reported until now, such as Anxa2, Atf6, and so on. These genes were involved in many pathways, such as peroxisome proliferator activated receptor signaling pathway. Conclusions: Gene expression changes induced by metformin were in support of the improvement of glucolipid metabolism and insulin resistance in KKAy mice. These findings expanded our knowledge of pharmacological action of metformin, and provided the potential novel insights and interesting information about the molecules involved in the antidiabetic effects of metformin. (C) 2016 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences.