Electroacupuncture at "Zusanli"(ST36) ameliorates tau hyperphosphorylation in pancreas and hippocampus of diabetic rats

Abstract

To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) on the phosphorylated tau levels in pancreas and hippocampus of type 2 diabetes mellitus (T2DM) rats，so as to explore the underlying mechanism of EA in diabetic demention rats. Forty-eight male Sprague-Dawley rats were randomly divided into control, model and EA groups, with 16 rats in each group. The T2DM model was established by 6 weeks of high-fat, high-sugar diet as well as intrape-ritoneal injection of streptozocin (STZ) solution (35 mg/kg). After that, EA (2 Hz, 0.1 mA) was applied to unilateral "Zusanli"(ST36) for 30 min, once a day, 6 times a week for 4 weeks. The survival rate was recorded every week, and the fasting blood glucose (FBG) was detected on the 1st, 6th and 11th week. The level of serum insulin (INS) was measured by using ELISA. The morphological structure of pancreas islet was observed by H.E. staining. The expressions of phosphorylated tau at the sites of Ser 396 (pS396) and Thr 231 (pT231), total tau (Tau5), phosphorylated glycogen synthase kinase-3β (pGSK-3β) and total glycogen synthase kinase-3β (GSK-3β) in pancreas and hippocampus were detected by Western blot. The expression and distribution of pS396 and pT231 in pancreas and hippocampus were assayed with immunohistochemistry. Compared with the control group, the survival rate presented a significant decline, the contents of FBG and INS were obviously higher(P<0.01), and the structure of the pancreas islet appeared shrunken, obscure and disordered in the model group. Furthermore, the levels of pS396, pT231 in pancreas and hippocampus were obviously higher in the model group(P<0.01)，while the level of pGSK-3β in pancreas and hippocampus was significantly lower in the model group(P<0.01). In comparison with the model group, the survival rate of EA group was higher. Following 4 weeks' interventions, the enhanced levels of tau phosphorylation and GSK-3β activity in pancreas and hippocampus were partly reversed in the EA group compared to the model group(P<0.05，P<0.01). EA at ST36 can reduce the level of tau phosphorylation via regulating the activity of GSK-3β in the pancreas and hippocampus of T2DM rats, which may be related with the effect of EA on the brain function in T2DM rats.