Saltar al contenido
Merck
  • Noncanonical activation of Akt/protein kinase B in {beta}-cells by the incretin hormone glucose-dependent insulinotropic polypeptide.

Noncanonical activation of Akt/protein kinase B in {beta}-cells by the incretin hormone glucose-dependent insulinotropic polypeptide.

The Journal of biological chemistry (2009-02-24)
Scott B Widenmaier, Arthur V Sampaio, T Michael Underhill, Christopher H S McIntosh
RESUMEN

Therapeutics based on the actions of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), have recently been introduced for the treatment of type 2 diabetes mellitus. The serine/threonine kinase Akt is a major mediator of incretin action on the pancreatic islet, increasing beta-cell mass and function and promoting beta-cell survival. The mechanisms underlying incretin activation of Akt are thought to involve an essential phosphoinositide 3-kinase-mediated phosphorylation of threonine 308, similar to the prototypical Akt activator, insulin-like growth factor-I (IGF-I). In this study, using activity assays on immunoprecipitated Akt, we discovered that GIP and GLP-1 were capable of stimulating Akt in the INS-1 beta-cell line and isolated mouse islets via a mechanism that did not require phosphoinositide 3-kinase or phosphorylation of Thr(308) and Ser(473), and this pathway involved the production of cAMP. Furthermore, we found that GIP stimulated anti-apoptotic signaling via this alternate mode of Akt activation. We conclude that incretins can activate Akt via a novel noncanonical mechanism that may provide an alternative therapeutic target for the treatment of type 2 diabetes mellitus and have broader implications for Akt physiology in human health and disease.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Millipore
Cóctel de inhibidores de proteasas, juego III, sin EDTA, Protease inhibitor cocktail III, EDTA-free for inhibiting aspartic, cysteine, and serine proteases as well as aminopeptidases in mammalian cells and tissues.