Down-regulation of hepatic HNF4alpha gene expression during hyperinsulinemia via SREBPs.

ABSTRACT: Mutations in the coding region of hepatocyte nuclear factor 4alpha (HNF4alpha), and its upstream promoter (P2) that drives expression in the pancreas, are known to lead to maturity-onset diabetes of the young 1 (MODY1). HNF4alpha also controls gluconeogenesis and lipid metabolism in the liver, where the proximal promoter (P1) predominates. However, very little is known about the role of hepatic HNF4alpha in diabetes. Here, we examine the expression of hepatic HNF4alpha in two diabetic mouse models, db/db mice (type 2, insulin resistant) and streptozotocin-treated mice (type 1, insulin deficient). We found that the level of HNF4alpha protein and mRNA was decreased in the liver of db/db mice but increased in streptozotocin-treated mice. Because insulin increases the activity of sterol regula

SUBMITTER: Xie X 

PROVIDER: S-EPMC2667705 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature