| First Author | Higuchi S | Year | 2019 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 316 |
| Issue | 3 | Pages | E410-E417 |
| PubMed ID | 30562059 | Mgi Jnum | J:273894 |
| Mgi Id | MGI:6283185 | Doi | 10.1152/ajpendo.00035.2018 |
| Citation | Higuchi S, et al. (2019) EP4 receptor-associated protein regulates gluconeogenesis in the liver and is associated with hyperglycemia in diabetic mice. Am J Physiol Endocrinol Metab 316(3):E410-E417 |
| abstractText | Prostaglandin E2 receptor 4-associated protein (EPRAP) is a key molecule in suppressing inflammatory responses in macrophages. EPRAP is expressed not only in macrophages but also in hepatocytes; however, the role of EPRAP in hepatocytes has not yet been defined. To examine the physiological role of hepatic EPRAP in mice, we performed the glucose tolerance test and the hyperinsulinemic-euglycemic clamp in high-fat sucrose diet (HFSD)-fed wild-type (WT) and Eprap null mice. We evaluated the contribution of EPRAP to gluconeogenesis by pyruvate tolerance test and primary hepatocyte experiments. Furthermore, lentivirus-expressing Eprap-specific small-hairpin RNA was injected in db/ db mice. HFSD-fed Eprap null mice had significantly lower blood glucose levels than HFSD-fed WT mice. Eprap null mice also had low glucose levels after fasting or pyruvic acid injection. Moreover, primary hepatocytes from Eprap-deficient mice showed decreased glucose production and lower expression of the Phosphoenol pyruvate carboxykinase and Glucose 6-phosphatase genes. Lentivirus-mediated hepatic Eprap suppression decreased glucose levels and the expression of gluconeogenic genes in db/ db mice. We conclude that EPRAP regulates gluconeogenesis in hepatocytes and is associated with hyperglycemia in diabetic mice. Our data suggest that suppression of EPRAP could be a novel strategy for the treatment of diabetes. |
