Regulation of hepatic energy metabolism and gluconeogenesis by BAD
| Autor: | Klaudia Polak, Sheene Kim, Jill K. Fisher, Gary W. Cline, Hu Huang, Benjamin Szlyk, Dae Ho Lee, Gerald I. Shulman, Alfredo Giménez-Cassina, Nika N. Danial, Alberto Distefano, Kirsten Robertson, Marina Godes, Muhammed A. Yildirim, Cheol Soo Choi, Ameya Kulkarni, Varman T. Samuel, Elaura Patton, Young-Bum Kim, Mayowa A. Osundiji, Luisa Garcia-Haro, Jessica Wiwczar, Elizabeth A. Lane |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Physiology medicine.medical_treatment Biology Article Mice Insulin resistance Internal medicine medicine Animals Glycolysis Phosphorylation Molecular Biology Beta oxidation Glucokinase Insulin Gluconeogenesis Cell Biology Metabolism medicine.disease Mice Mutant Strains Endocrinology Liver bcl-Associated Death Protein Energy Metabolism Homeostasis |
| Zdroj: | Cell metabolism. 19(2) |
| ISSN: | 1932-7420 |
| Popis: | Summary The homeostatic balance of hepatic glucose utilization, storage, and production is exquisitely controlled by hormonal signals and hepatic carbon metabolism during fed and fasted states. How the liver senses extracellular glucose to cue glucose utilization versus production is not fully understood. We show that the physiologic balance of hepatic glycolysis and gluconeogenesis is regulated by Bcl-2-associated agonist of cell death (BAD), a protein with roles in apoptosis and metabolism. BAD deficiency reprograms hepatic substrate and energy metabolism toward diminished glycolysis, excess fatty acid oxidation, and exaggerated glucose production that escapes suppression by insulin. Genetic and biochemical evidence suggests that BAD's suppression of gluconeogenesis is actuated by phosphorylation of its BCL-2 homology (BH)-3 domain and subsequent activation of glucokinase. The physiologic relevance of these findings is evident from the ability of a BAD phosphomimic variant to counteract unrestrained gluconeogenesis and improve glycemia in leptin-resistant and high-fat diet models of diabetes and insulin resistance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|