Diabetes is such a clinical condition that blood glucose level is increased due to increase of insulin resistance in a peripheral tissue or reduction of insulin secretion. The disease leads to various serious complications, and thus the diabetes has to be treated with a medicament. Conventionally, sulfonylurea agents, phenylalanine derivatives, α-glucosidase inhibitors, biguanides, thiazolidine derivatives, insulin, etc. have been used as antidiabetic agents (Non-Patent Document 1: Sheehan et al., Clinical Medicine & Research, 1, 189, (2003)).
In recent years, compounds capable of enhancing the glucose uptake activity of a peripheral cell such as a adipocyte (hereinafter referred to as the glucose uptake enhancers) have been known (Patent Document 1: WO 02/44180; Patent Document 2: WO 2005/068467; Patent Document 3: WO 2005/042536; Patent Document 4: WO 2006/118341). These compounds are indicated to enhance the glucose uptake activity of a adipocyte, etc. even in the absence of insulin, and further to exhibit a hypoglycemic effect in a diabetic model animal. The above medicaments other than insulin, conventionally used as the antidiabetic agent, cannot enhance the glucose uptake activity of a adipocyte, etc. in the absence of insulin. Thus, the glucose uptake enhancers described in Patent Documents 1 to 4 are considered to be useful as the antidiabetic agent. However, the mechanisms of action of these glucose uptake enhancers have not been known and reported.
It has been known that a protein Akt has to be phosphorylated (in Ser473) to achieve the glucose uptake effect of insulin (Non-Patent Document 2: Hajduch et al., FEBS Letters, 492, 199, (2001)). However, the relationship between the effects of the above glucose uptake enhancers and the Akt phosphorylation has not been known.    Patent Document 1: WO 02/44180    Patent Document 2: WO 2005/068467    Patent Document 3: WO 2005/042536    Patent Document 4: WO 2006/118341    Non-Patent Document 1: Sheehan et al., Clinical Medicine & Research, 1, 189, (2003)    Non-Patent Document 2: Hajduch et al., FEBS Letters, 492, 199, (2001)