Constitutively active Akt1 expression in mouse pancreas requires S6 kinase 1 for insulinoma formation.

ABSTRACT: Factors that promote pancreatic beta cell growth and function are potential therapeutic targets for diabetes mellitus. In mice, genetic experiments suggest that signaling cascades initiated by insulin and IGFs positively regulate beta cell mass and insulin secretion. Akt and S6 kinase (S6K) family members are activated as part of these signaling cascades, but how the interplay between these proteins controls beta cell growth and function has not been determined. Here, we found that although transgenic mice overexpressing the constitutively active form of Akt1 under the rat insulin promoter (RIP-MyrAkt1 mice) had enlarged beta cells and high plasma insulin levels, leading to improved glucose tolerance, a substantial proportion of the mice developed insulinomas later in life, which caused de

SUBMITTER: Alliouachene S 

PROVIDER: S-EPMC2564609 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature