Identification of a novel gene, MSAG, regulated by high levels of glucose and insulin.

Identification and characterization of novel genes involved in derangement of metabolisms of glucose and triglycerides are important in understanding the development of metabolic syndrome (MS) and atherosclerosis. Model rats with certain phenotypes of MS were fed a high-carbohydrate diet. The rat hepatic subtracted cDNA libraries were constructed and screened. A novel cDNA of full length was identified by screening of a human hepatic cDNA library with a mixture of probes of the differentially expressed fragments from the rat hepatic subtracted cDNA libraries. The corresponding gene of the cDNA was temporarily named metabolic syndrome-associated gene (MSAG). The predicted protein encoded by MSAG contains 110 amino acids and has a theoretical molecular weight of 11667.04 and an isoelectric point of 4.91. Compared with the housekeeping gene of β-actin, MSAG had low transcription activity. However, the mRNA level of MSAG in HepG2 cells, a human hepatoma cell line, was significantly increased by glucose and decreased by insulin concentrations higher than physiological levels. These results suggest that MSAG may be involved in the metabolism and/or its regulation of glucose, the functioning of insulin under non-physiological conditions, and further in the development of metabolic syndrome.