Abstract: A method for identifying a target protein of a compound having a pharmacological action by detecting a tertiary structural change of a target protein by binding a compound having a pharmacological action to a target protein with the use of a molecular chaperone protein having a characteristic of binding to a protein by recognizing a tertiary structural change of the protein is disclosed. Further, a method for screening a therapeutic agent for diabetes using a target protein of biguanide which is a therapeutic agent for diabetes and was found by the identification method, a screening tool which can be used in the screening method and a pharmaceutical composition for treating diabetes containing a substance obtained by the screening method are disclosed.

Abstract: A method for identifying a target protein of a compound having a pharmacological action by detecting a tertiary structural change of a target protein by binding a compound having a pharmacological action to a target protein with the use of a molecular chaperone protein having a characteristic of binding to a protein by recognizing a tertiary structural change of the protein is disclosed. Further, a method for screening a therapeutic agent for diabetes using a target protein of biguanide which is a therapeutic agent for diabetes and was found by the identification method, a screening tool which can be used in the screening method and a pharmaceutical composition for treating diabetes containing a substance obtained by the screening method are disclosed.

Abstract: A novel polypeptide, a polynucleotide, an expression vector, a cell transfected with the expression vector, a method for screening an insulin resistance improving agent and a carbohydrate metabolism improving agent, and a method for producing a pharmaceutical composition are provided. The polypeptide is useful in screening an insulin resistance improving agent and a carbohydrate metabolism improving agent. When the polypeptide is overexpressed in a fat cell, the activity of Akt2 is reduced. Fat cells express the polypeptide. The polynucleotide encodes the polypeptide. The expression vector includes the polynucleotide. The screening method uses the polypeptide to screen for an insulin resistance improving agent and a carbohydrate metabolism improving agent. The production method uses the substance obtained by the screening method as the active ingredient of the pharmaceutical composition. The pharmaceutical composition is useful for insulin resistance improvement and carbohydrate metabolism improvement.

Abstract: The present invention provides a method of screening a drug for improving type 2 diabetes. A protein CbAP40 binding to c-Cbl is found out. It is further found out that mouse CbAP40 gene shows a remarkable increase in expression amount in the muscle of diabetes model mice compared with a normal individual and glucose incorporation is inhibited by overexpressing human CbAP40 gene in a muscle-origin cell, thereby clarifying that the above protein is a factor causative of diabetic conditions. Moreover, the promoter region of human CbAP40 gene is identified and it is clarified that a transcription-inducing activity originating in this promoter region is inhibited by a thiazolidine derivative that improves insulin resistance. Based on these findings, systems for screening a substance having an effect of improving insulin resistance, in which a change of promoter activity and a change in the interaction between c-Cbl and CbAP40 are indicators, are constructed.

Abstract: A novel polypeptide which is useful in screening of an agent for improving insulin resistance and an agent for improving glucose metabolism, a polynucleotide encoding the polypeptide, an expression vector comprising the polynucleotide, and a cell transformed with the expression vector are disclosed. The polypeptide is a protein expressed in skeletal muscle. When the protein is overexpressed, incorporation of sugar into a cell is inhibited. A method for screening of an agent for improving insulin resistance and/or an agent for improving glucose metabolism in which the polypeptide is used, and a method for producing a pharmaceutical composition for insulin resistance and/or glucose metabolism improvement comprising a substance obtained according to the method for screening as an active ingredient are also disclosed.

Abstract: A novel polypeptide useful in screening an insulin resistance improving agent and a carbohydrate metabolism improving agent, a polynucleotide coding for the aforementioned polypeptide, an expression vector comprising the aforementioned polynucleotide, and a cell transfected with the aforementioned expression vector are disclosed. The aforementioned polypeptide is a protein which is expressed in fat, and the activity of Akt2 is reduced in a fat cell in which the protein is highly expressed. A method for screening an insulin resistance improving agent and a carbohydrate metabolism improving agent using the aforementioned polypeptide, and a method for producing a pharmaceutical composition for insulin resistance improvement and carbohydrate metabolism improvement, which uses a substance obtained by said screening method as the active ingredient, are disclosed.

Abstract: A novel polypeptide which is useful in screening of an agent for improving insulin resistance and an agent for improving glucose metabolism, a polynucleotide encoding the polypeptide, an expression vector comprising the polynucleotide, and a cell transformed with the expression vector are disclosed. The polypeptide is a protein expressed in skeletal muscle. When the protein is overexpressed, incorporation of sugar into a cell is inhibited. A method for screening of an agent for improving insulin resistance and/or an agent for improving glucose metabolism in which the polypeptide is used, and a method for producing a pharmaceutical composition for insulin resistance and/or glucose metabolism improvement comprising a substance obtained according to the method for screening as an active ingredient are also disclosed.

Abstract: A method for identifying and screening a novel substance promoting the transcription induction activity of PPAR? and improving insulin resistance by promoting the interaction between PPAR promoting the transcription induction activity of PPAR? and p68 RNA helicase and/or promoting the expression of p68RNA helicase is disclosed. The method is a new type method for screening an agent for improving insulin resistance by promoting the transcription induction activity of PPAR? which is different from the conventional PPAR agonist. Furthermore, the method for producing a pharmaceutical composition for improving insulin resistance which comprises the substance obtainable by the above method for screening as an active ingredient is disclosed.

Abstract: Disclosing a method for screening a protein interactive with PPAR in a ligand-dependent manner, works as a useful tool for screening a drug ameliorating insulin resistance. By the method, ECHLP as a main action ligand-dependent PPAR binding molecule, FLJ13111 as a main action ligand-selective factor interactive with PPAR? and AOP2 as an adverse action ligand-dependent PPAR binding molecule were obtained. By using ECHLP interactive with PPAR, FLJ13111 interactive with PPAR and AOP2 interactive with PPAR, a screening system for a drug ameliorating insulin resistance is constructed and disclosed, the drug giving selectively the main action with no occurrence of the adverse action.