| First Author | Matsuoka TA | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 12 | Pages | 7647-57 |
| PubMed ID | 25645923 | Mgi Jnum | J:264471 |
| Mgi Id | MGI:6196995 | Doi | 10.1074/jbc.M114.595579 |
| Citation | Matsuoka TA, et al. (2015) Preserving Mafa expression in diabetic islet beta-cells improves glycemic control in vivo. J Biol Chem 290(12):7647-57 |
| abstractText | The murine Mafa transcription factor is a key regulator of postnatal islet beta-cell activity, affecting insulin transcription, insulin secretion, and beta-cell mass. Human MAFA expression is also markedly decreased in islet beta-cells of type 2 diabetes mellitus (T2DM) patients. Moreover, levels are profoundly reduced in db/db islet beta-cells, a mouse model of T2DM. To examine the significance of this key islet beta-cell-enriched protein to glycemic control under diabetic conditions, we generated transgenic mice that conditionally and specifically produced Mafa in db/db islet beta-cells. Sustained expression of Mafa resulted in significantly lower plasma glucose levels, higher plasma insulin, and augmented islet beta-cell mass. In addition, there was increased expression of insulin, Slc2a2, and newly identified Mafa-regulated genes involved in reducing beta-cell stress, like Gsta1 and Gckr. Importantly, the levels of human GSTA1 were also compromised in T2DM islets. Collectively, these results illustrate how consequential the reduction in Mafa activity is to islet beta-cell function under pathophysiological conditions. |
