| Autor: |
Hyekyung Yang, Qing Li, Jong-Hwan Lee, Yan Shu |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
|
| Zdroj: |
International Journal of Biological Sciences, Vol 8, Iss 6, Pp 791-801 (2012) |
| Druh dokumentu: |
article |
| ISSN: |
1449-2288 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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