| First Author | Gillespie JR | Year | 2013 |
| Journal | Endocrinology | Volume | 154 |
| Issue | 10 | Pages | 3702-18 |
| PubMed ID | 23904355 | Mgi Jnum | J:203283 |
| Mgi Id | MGI:5525948 | Doi | 10.1210/en.2013-1155 |
| Citation | Gillespie JR, et al. (2013) GSK-3beta function in bone regulates skeletal development, whole-body metabolism, and male life span. Endocrinology 154(10):3702-18 |
| abstractText | Glycogen synthase kinase 3 beta (GSK-3beta) is an essential negative regulator or "brake" on many anabolic-signaling pathways including Wnt and insulin. Global deletion of GSK-3beta results in perinatal lethality and various skeletal defects. The goal of our research was to determine GSK-3beta cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6-kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b knockout) in skeletal cells. Mutant mice exhibit decreased body fat and postnatal bone growth, as well as delayed development of several skeletal elements. Surprisingly, the mutant mice display decreased circulating glucose and insulin levels despite normal expression of GSK-3beta in metabolic tissues. We showed that these effects are due to an increase in global insulin sensitivity. Most of the male mutant mice died after weaning. Prior to death, blood glucose changed from low to high, suggesting a possible switch from insulin sensitivity to resistance. These male mice die with extremely large bladders that are preceded by damage to the urogenital tract, defects that are also seen type 2 diabetes. Our data suggest that skeletal-specific deletion of GSK-3beta affects global metabolism and sensitizes male mice to developing type 2 diabetes. |
