Effect of insulin treatment on streptozotocin-induced bone loss in female mice. The levels of plasma PAI-1 (A) and PAI-1 mRNA in liver (B), BMDs (total, trabecular, and cortical), and bone strength index in tibia (C) in control female mice and diabetic female mice treated with or without insulin for 4 weeks. Results are expressed relative
to β-actin mRNA values and expressed as means ± SEM. **P < 0.01 (n = 6 in each group). Proposed hypothesis for the role of PAI-1 in the pathogenesis of diabetic osteoporosis in female mice
(D): Diabetic state induces an increase in PAI-1 expression in the liver, resulting in an elevation of circulating PAI-1 levels
in female mice. An elevated circulating PAI-1 impairs osteoblast differentiation and mineralization. Furthermore, it promotes
adipogenesis in bone tissues. These cascades may lead to diabetic osteoporosis in female mice.