Abstract
This study is designed to evaluate the treatment effect of electroacupuncture (EA) in chronic steroid induced insulin resistant rat model. An alternative therapy is explored to reduce the chronic steroid induced insulin resistance.The aim of this study is to determine (1) if EA treatment can produce hypoglycemic effect and (2) inhibit the development of glucocorticoid-altered insulin sensitivity in chronic status and to (3) explore the mechanisms of EA by assaying plasma FFAs and proteins of insulin signal pathway. Intravenous glucose tolerance test (IVGTT) and insulin challenge test (ICT) were applied to evaluate the effect of EA on steroid induced insulin resistance (SIIR) rats. Finally, this study evaluates proteins of insulin signaling pathway to investigate the mechanisms by which EA improves the insulin resistance of SIIR rats. We hypothesized that electroacupuncture can produce a hypoglycemic effect in chronic steroid induced insulin resistance diabetes rat model. A diabetes rat model was created by using clinical-like dose dexamethasone, 1 mg/kg, i.p. once a day chronic to induce insulin resistance for 5 days. Then the steroid induced insulin resistant (SIIR) rats were randomly divided into SIIR+EA group and SIIR group. Plasma glucose, insulin challenge test (ICT) and intravenous glucose tolerance test (ivGTT) were used to test the change of plasma glucose levels between SIIR+EA group and SIIR group. The plasma free fatty acids (FFA) and related proteins of the insulin signaling pathway, such as IRS-1 and GLUT4 were also checked to explore the effect of EA on recovering insulin sensitivity of SIIR rats. The results showed that EA could decrease the FFA level and increase insulin sensitivity in SIIR rats. Further clinical studies are needed to determine whether EA can be an alternative and effective treatment for patients for whom chronic usage of dexamethasone is needed by reducing insulin resistance. Data on expression of all genes in a biological sample can be achieved in one experiment using the microarray method, the results of which can be analyzed to determine the potential pathways involved in a given process and identify potential therapeutic targets. Then the microarray analysis experiment was done to explore the possible signaling pathway related to hypoglycemic effect induced by the EA. Previous animal studies have reported a hypoglycemic effect of EA and suggested that the mechanisms are closely related to intracellular signaling pathways. The aim of this study was to screen potential for intracellular signaling pathways that are upregulated by EA at bilateral ST36 in rats with diabetes using microarray analysis. Streptozotocin (STZ) - induced diabetic rats were randomly assigned to experimental (EA, n=8) or control (non-EA, n=8) groups. Plasma glucose levels were measured at baseline, 30 and 60 minutes, and microarray analysis was performed on samples of the gastrocnemius muscle. Relative to baseline values, EA significantly reduced plasma levels of glucose at 30 and 60 minutes. The microarray pathway analysis showed that cell adhesion molecules and type 1 DM gene sets were both upregulated in EA versus non-EA groups (p<0.05). Cell adhesion molecules might be related to the hypoglycemic effect induced by EA in rats with STZ-induced type I diabetes. Future research will be required to examine the involvement of related intracellular signaling pathways.