Glycogen synthase kinase 3 beta (GSK-3β) is an essential negative regulator or "brake" on many anabolic-signalling pathways including Wnt and insulin. Global deletion of GSK-3β results in perinatal lethality and various skeletal defects. The goal of our research was to determine GSK-3β cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6Kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b KO) 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-3β in metabolic tissues. We showed that these effects are due to an increase in global insulin sensitivity. Most of the male mutant mice died post 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 II diabetes. Our data suggests that skeletal-specific deletion of GSK-3β affects global metabolism and sensitizes male mice to developing type II diabetes.