title: The transcription factor CREB has no non-redundant functions in hepatic glucose metabolism in mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, 12-126 Translational Research Center, 3400 Civic Center Boulevard, Philadelphia, PA, 19104-6145, USA.
authors.forename: Dolim
authors.initials: D
authors.lastname: Lee
authors.forename: John
authors.initials: J
authors.lastname: Le Lay
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D005951:Glucose Tolerance Test; D022781:Hepatocytes / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism*; D051379:Mice
chemical_list: D001786:Blood Glucose; D017362:Cyclic AMP Response Element-Binding Protein; D005947:Glucose