Diabetes risk gene and Wnt effector Tcf7l2/TCF4 controls hepatic response to perinatal and adult metabolic demand

ABSTRACT: Most studies on TCF7L2 SNP variants in the pathogenesis of type 2 diabetes (T2D) focus on a role of the encoded transcription factor TCF4 in β-cells. Here, a mouse genetics approach shows that removal of TCF4 from β-cells does not affect their function, while manipulating TCF4 levels in the liver has major effects on metabolism. In Tcf7l2-/- mice, the immediate postnatal surge in liver metabolism does not occur. Consequently, pups die due to hypoglycemia. Combining chromatin immunoprecipitation with gene expression profiling, we identify a TCF4-controlled metabolic gene program that is acutely activated in the postnatal liver. In concordance, adult liver-specific Tcf7l2 knockout mice show reduced hepatic glucose production during fasting and display improved glucose homeostasis when main

ORGANISM(S): Mus musculus

SUBMITTER: Vivian Li 

PROVIDER: E-GEOD-41284 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress