| First Author | Lee D | Year | 2014 |
| Journal | Diabetologia | Volume | 57 |
| Issue | 6 | Pages | 1242-8 |
| PubMed ID | 24595858 | Mgi Jnum | J:210887 |
| Mgi Id | MGI:5572846 | Doi | 10.1007/s00125-014-3203-2 |
| Citation | Lee D, et al. (2014) The transcription factor CREB has no non-redundant functions in hepatic glucose metabolism in mice. Diabetologia 57(6):1242-8 |
| abstractText | AIMS/HYPOTHESIS: Excessive hepatic glucose production is a hallmark of insulin resistance in type 2 diabetes. The cAMP responsive transcription factor cAMP responsive element binding protein (CREB), thought to be a key activator of the hepatic gluconeogenic gene regulation programme, has been suggested as a therapeutic target to reduce glucose output by the liver. Here, we test directly the requirement for hepatocytic CREB for the maintenance of glucose homeostasis. METHODS: We derived mice with a Creb (also known as Creb1) loxP allele for conditional, cell-type specific gene ablation. Hepatocyte-specific deletion of Creb was induced by injecting Creb (loxP/loxP) mice with Cre recombinase expression adeno-associated virus. RESULTS: Strikingly, we found no difference in fed and fasted glucose levels, or in glucose, insulin and glucagon tolerance in mice fed a normal chow or a high-fat diet. In addition, mRNA levels of liver-specific genes, including several CREB target genes involved in gluconeogenesis, were not affected by CREB deficiency in the liver. CONCLUSION/INTERPRETATION: Our data show that CREB has no non-redundant functions in hepatic glucose metabolism, and is therefore not likely to be a useful target for the development of glucose-lowering drugs. |
