The prolonged use of therapeutic glucocorticoids is associated with a range of adverse effects (figure
1). The detrimental effects on bone have received the greatest focus and there are now a range of therapeutic strategies available to reduce the negative effects of glucocorticoids on bone [1].
Endogenous or exogenous glucocorticoid excess is also associated with other serious clinical features such as the development of insulin resistance, impaired glucose tolerance and frank diabetes [2].
Glucocorticoids also cause changes in fat distribution favouring accumulation of central (visceral) fat at the expense of subcutaneous adipose tissue. Traditionally it has been thought that these adverse effects were mediated by direct effects of glucocorticoids on adipose tissue or …show more content…
This gene therapy was achieved through the use of hemodynamic tail vein injections to transfect hepatocytes in vivo with a plasmid containing osteocalcin and a control empty vector. The gene therapy was also designed to express a vector engineered to cause synthesis of a mutated osteocalcin protein which was incapable of being carboxylated. The expression of both of these forms of osteocalcin was examined since in other situations it had been observed that the hormonal effects of osteocalcin were primarily seen with the un- or under-carboxylated forms of osteocalcin rather than the carboxylated form [22]. Mice with heterotopic expression of osteocalcin had normal levels of osteocalcin under normal conditions but remain the normal osteocalcin levels in response to glucocorticoid treatment. In a manner similar to that seen in 11-HSD2 transgenic mice, the expression of osteocalcin protected mice against the development of glucose intolerance,
1). The detrimental effects on bone have received the greatest focus and there are now a range of therapeutic strategies available to reduce the negative effects of glucocorticoids on bone [1].
Endogenous or exogenous glucocorticoid excess is also associated with other serious clinical features such as the development of insulin resistance, impaired glucose tolerance and frank diabetes [2].
Glucocorticoids also cause changes in fat distribution favouring accumulation of central (visceral) fat at the expense of subcutaneous adipose tissue. Traditionally it has been thought that these adverse effects were mediated by direct effects of glucocorticoids on adipose tissue or …show more content…
This gene therapy was achieved through the use of hemodynamic tail vein injections to transfect hepatocytes in vivo with a plasmid containing osteocalcin and a control empty vector. The gene therapy was also designed to express a vector engineered to cause synthesis of a mutated osteocalcin protein which was incapable of being carboxylated. The expression of both of these forms of osteocalcin was examined since in other situations it had been observed that the hormonal effects of osteocalcin were primarily seen with the un- or under-carboxylated forms of osteocalcin rather than the carboxylated form [22]. Mice with heterotopic expression of osteocalcin had normal levels of osteocalcin under normal conditions but remain the normal osteocalcin levels in response to glucocorticoid treatment. In a manner similar to that seen in 11-HSD2 transgenic mice, the expression of osteocalcin protected mice against the development of glucose intolerance,