| Autor: |
Gao Sun, Gabriela da Silva Xavier, Tracy Gorman, Claire Priest, Antonia Solomou, David J. Hodson, Marc Foretz, Benoit Viollet, Pedro-Luis Herrera, Helen Parker, Frank Reimann, Fiona M. Gribble, Stephanie Migrenne, Christophe Magnan, Anna Marley, Guy A. Rutter |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Molecular Metabolism, Vol 4, Iss 4, Pp 277-286 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2212-8778 |
| DOI: |
10.1016/j.molmet.2015.01.006 |
| Popis: |
Aims/Hypothesis: Glucagon release from pancreatic alpha cells is required for normal glucose homoeostasis and is dysregulated in both Type 1 and Type 2 diabetes. The tumour suppressor LKB1 (STK11) and the downstream kinase AMP-activated protein kinase (AMPK), modulate cellular metabolism and growth, and AMPK is an important target of the anti-hyperglycaemic agent metformin. While LKB1 and AMPK have emerged recently as regulators of beta cell mass and insulin secretion, the role of these enzymes in the control of glucagon production in vivo is unclear. Methods: Here, we ablated LKB1 (αLKB1KO), or the catalytic alpha subunits of AMPK (αAMPKdKO, -α1KO, -α2KO), selectively in ∼45% of alpha cells in mice by deleting the corresponding flox'd alleles with a preproglucagon promoter (PPG) Cre. Results: Blood glucose levels in male αLKB1KO mice were lower during intraperitoneal glucose, aminoimidazole carboxamide ribonucleotide (AICAR) or arginine tolerance tests, and glucose infusion rates were increased in hypoglycemic clamps (p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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