| First Author | Chen WS | Year | 2009 |
| Journal | Mol Cell Biol | Volume | 29 |
| Issue | 11 | Pages | 3151-62 |
| PubMed ID | 19289493 | Mgi Jnum | J:149156 |
| Mgi Id | MGI:3847832 | Doi | 10.1128/MCB.01792-08 |
| Citation | Chen WS, et al. (2009) Leptin deficiency and beta-cell dysfunction underlie type 2 diabetes in compound Akt knockout mice. Mol Cell Biol 29(11):3151-62 |
| abstractText | Phenotypic analyses of mice null for the individual Akt isoforms suggested that they are functionally distinct and that only Akt2 plays a role in diabetes. We show here that Akt isoforms play compensatory and complementary roles in glucose homeostasis and diabetes. Insulin resistance in Akt2(-/-) mice was inhibited by haplodeficiency of Pten, suggesting that other Akt isoforms can compensate for Akt2 function. Haplodeficiency of Akt1 in Akt2(-/-) mice, however, converts prediabetes to overt type 2 diabetes, which is also reversed by haplodeficiency of Pten. Akt3 does not appear to contribute significantly to diabetes. Overt type 2 diabetes in Akt1(+/-) Akt2(-/-) mice is manifested by hyperglycemia due to beta-cell dysfunction combined with impaired glucose homeostasis due to markedly decreased leptin levels. Restoring leptin levels was sufficient to restore normal blood glucose and insulin levels in Akt1(+/-) Akt2(-/-) and Akt2(-/-) mice, suggesting that leptin-deficiency is the predominant cause of diabetes in these mice. These results uncover a new mechanism linking Akt to diabetes, provide a therapeutic strategy, and show that diabetes induced as a consequence of cancer therapy, via Akt inhibition, could be reversed by leptin therapy. |
