| First Author | Yang H | Year | 2012 |
| Journal | Int J Biol Sci | Volume | 8 |
| Issue | 6 | Pages | 791-801 |
| PubMed ID | 22719219 | Mgi Jnum | J:287951 |
| Mgi Id | MGI:6402967 | Doi | 10.7150/ijbs.4568 |
| Citation | Yang H, et al. (2012) Reduction in Tcf7l2 expression decreases diabetic susceptibility in mice. Int J Biol Sci 8(6):791-801 |
| abstractText | OBJECTIVE: The WNT signaling pathway effector gene TCF7L2 has been associated with an increased risk of type 2 diabetes. However, it remains unclear how this gene affects diabetic pathogenesis. The goal of this study was to investigate the effects of Tcf7l2 haploinsufficiency on metabolic phenotypes in mice. EXPERIMENTAL DESIGN: Tcf7l2 knockout (Tcf7l(-)/(-)) mice were generated. Because of the early mortality of Tcf7l2(-)/(-) mice, we characterized the metabolic phenotypes of heterozygous Tcf7l2(+)/(-) mice in comparison to the wild-type controls. The mice were fed a normal chow diet or a high fat diet (HFD) for 9 weeks. RESULTS: The Tcf7l2(+)/(-) mice showed significant differences from the wild-type mice with regards to body weight, fasting glucose and insulin levels. Tcf7l2(+)/(-) mice displayed improved glucose tolerance. In the liver of Tcf7l2(+)/(-) mice fed on the HFD, reduced lipogenesis and hepatic triglyceride levels were observed when compared with those of wild-type mice. Furthermore, the Tcf7l2(+)/(-) mice fed on the HFD exhibited decreased peripheral fat deposition. Immunohistochemistry in mouse pancreatic islets showed that endogenous expression of Tcf7l2 was upregulated in the wild-type mice, but not in the Tcf7l2(+)/(-) mice, after feeding with the HFD. However, the haploinsufficiency of Tcf7l2 in mouse pancreatic islets resulted in little changes in glucose-stimulated insulin secretion. CONCLUSION: These results suggest that decreased expression of Tcf7l2 confers reduction of diabetic susceptibility in mice via regulation on the metabolism of glucose and lipid. |
