Ablation of PDK1 in pancreatic β cells induces diabetes as a result of loss of β cell mass
| Autor: | Yoshito Fujimoto, Tetsuo Noda, Masato Kasuga, Yoshiaki Kido, Hitoshi Okamura, Tomokazu Matsuda, Yutaka Shigeyama, Pedro Luis Herrera, Akihiko Takeda, Naoko Hashimoto, Daisuke Tsuchihashi, Akihiko Nishizawa, Wataru Ogawa, Shun-ichiro Asahara, Tohru Uchida, Karen C. Arden |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Islets of Langerhans/ enzymology/ pathology FOXO1 Protein Serine-Threonine Kinases Biology Diabetes Mellitus Experimental 3-Phosphoinositide-Dependent Protein Kinases Diabetes Mellitus Experimental/enzymology/ genetics/pathology Islets of Langerhans Mice Internal medicine Insulin receptor substrate Genetics medicine Animals Glucose homeostasis ddc:616 Mice Knockout geography geography.geographical_feature_category Insulin Islet Protein-Serine-Threonine Kinases/ genetics medicine.anatomical_structure Endocrinology Signal transduction Beta cell Pancreas Signal Transduction |
| Zdroj: | Nature Genetics, Vol. 38, No 5 (2006) pp. 589-593 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng1774 |
| Popis: | The total mass of islets of Langerhans is reduced in individuals with type 2 diabetes, possibly contributing to the pathogenesis of this condition. Although the regulation of islet mass is complex, recent studies have suggested the importance of a signaling pathway that includes the insulin or insulin-like growth factor-1 receptors, insulin receptor substrate and phosphatidylinositol (PI) 3-kinase. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a serine-threonine kinase that mediates signaling downstream of PI 3-kinase. Here we show that mice that lack PDK1 specifically in pancreatic beta cells (betaPdk1-/- mice) develop progressive hyperglycemia as a result of a loss of islet mass. The mice show reductions in islet density as well as in the number and size of cells. Haploinsufficiency of the gene for the transcription factor Foxo1 resulted in a marked increase in the number, but not the size, of cells and resulted in the restoration of glucose homeostasis in betaPdk1-/- mice. These results suggest that PDK1 is important in maintenance of pancreatic cell mass and glucose homeostasis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|