The effects of Diabetes Mellitus on brain insulin-PI3K signaling pathway and tau hyperphosphorylation

Diabetes Mellitus is a chronic hyperglycemic metabolic disease leading to disorders of carbohydrate, lipid and protein metabolism due to relative or definite deficiency of insulin function and/or insulin hormon secretion. Following the demonstration of insulin receptors in the brain, insulin appears to play a role in brain physiology, and disturbances of cerebral insulin signalling and glucose homeostasis are implicated in brain pathology. In our study we aimed to investigate the possible effects of Diabetes on the accumulation of the main pathologic hallmarks of Alzheimer Disease, tau hyperphosphorylation, and the relationship with insulin signaling pathways molecules in rat brain tissue. Wistar rats were assigned randomly into three goups, Group I; control, Group II; diabetes (DM), Group III; diabetes+insulin (DM+I). Serum insulin and Amyloid ß 1-42 (Aß) levels were measured by ELISA. Using Western blot there were shown alterations of the insulin receptor (IR) signaling cascade at the level of PKB/Akt, GSK-3 and tau protein in the hippocampus, 12 weeks after i.p injection of stz in rats. Plasma Aß levels were significantly increased in diabetes compared to control. And also, diabetes induced an increase of tau phosphorylation at the Thr 231 site. Our results pointed out an increased Aß levels and tau hyperphosphorylation, suggested that the defects of insulin signal transduction in brain that Diabetes Mellitus have an increase risk to develop Alzheimer Disease.