| First Author | Iwasaki Y | Year | 2009 |
| Journal | Biochem Biophys Res Commun | Volume | 378 |
| Issue | 3 | Pages | 545-50 |
| PubMed ID | 19056350 | Mgi Jnum | J:142914 |
| Mgi Id | MGI:3822411 | Doi | 10.1016/j.bbrc.2008.11.105 |
| Citation | Iwasaki Y, et al. (2009) Nuclear SREBP-1a causes loss of pancreatic beta-cells and impaired insulin secretion. Biochem Biophys Res Commun 378(3):545-50 |
| abstractText | Transgenic mice expressing nuclear sterol regulatory element-binding protein-1a under the control of the insulin promoter were generated to determine the role of SREBP-1a in pancreatic beta-cells. Only low expressors could be established, which exhibited mild hyperglycemia, impaired glucose tolerance, and reduced plasma insulin levels compared to C57BL/6 controls. The islets isolated from the transgenic mice were fewer and smaller, and had decreased insulin content and unaltered glucagon staining. Both glucose- and potassium-stimulated insulin secretions were decreased. The transgenic islets consistently expressed genes for fatty acids and cholesterol synthesis, resulting in accumulation of triglycerides but not cholesterol. PDX-1, BetaEpsilonTauAlpha2, MafA, and IRS-2 were suppressed, partially explaining the loss and dysfunction of beta-cell mass. The transgenic mice on a high fat/high sucrose diet still exhibited impaired insulin secretion and continuous beta-cell growth defect. Therefore, nuclear SREBP-1a, even at a low level, strongly disrupts beta-cell mass and function. |
