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| Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta |
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| Author(s): Garofalo RS, Orena SJ, Rafidi K, Torchia AJ, Stock JL, Hildebrandt AL, Coskran T, Black SC, Brees DJ, Wicks JR, McNeish JD, Coleman KG |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 112 Issue: 2 Pages: 197-208 Published: JUL 2003 |
| Times Cited: 175 References: 63 |
| Abstract: The serine/threonine kinase Akt/PKB plays key roles in the regulation of cell growth, survival, and metabolism. It remains unclear, however, whether the functions of individual Akt/PKB isoforms are distinct. To investigate the function of Akt2/PKBbeta, mice lacking this isoform were generated. Both male and female Akt2/PKBbeta-null mice exhibit mild growth deficiency and an age-dependent loss of adipose tissue or lipoatrophy, with all observed adipose depots dramatically reduced by 22 weeks of age. Akt2/PKBbeta-deficient mice are insulin resistant with elevated plasma triglycerides. In addition, Akt2/PKBbeta-deficient mice exhibit fed and fasting hyperglycemia, hyperinsulinemia, glucose intolerance, and impaired muscle glucose uptake. In males, insulin resistance progresses to a severe form of diabetes accompanied by pancreatic beta cell failure. In contrast female Akt2/PKBbeta-deficient mice remain mildly hyperglycemic and hyperinsulinemic until at least one year of age. Thus, Akt2/PKBbeta-deficient mice exhibit growth deficiency similar to that reported previously for mice lacking Akt1/PKBalpha, indicating that both Akt2/PKBbeta and Akt1/PKBalpha participate in the regulation of growth. The marked hyperglycemia and loss of pancreatic P cells and adipose tissue in Akt2/PKBbeta-deficient mice suggest that Akt2/PKBbeta plays critical roles in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass for which other Akt/PKB isoforms are unable to fully compensate. |
| Document Type: Article |
| Language: English |
| Reprint Address: Garofalo, RS (reprint author), Pfizer Global, Res & Dev, MS 8220-3082,Eastern Point Rd, Groton, CT 06357 USA |
Addresses:
1. Pfizer Global, Res & Dev, Groton, CT 06357 USA |
| Publisher: AMER SOC CLINICAL INVESTIGATION INC, 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: 701YT |
| ISSN: 0021-9738 |
| DOI: 10.1172/JCI200316885 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |