Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction.

Objective: To explore the role of oxidative stress on glycogen synthase kinase-3 in lymphocytes of diabetes mellitus (DM) patients complicated with cerebral infarction (CI).

Materials and methods: A total of 186 DM patients were enrolled according to the inclusion criteria and exclusion criteria, including 89 DM patients alone (DM group) and 97 DM patients with CI (DM + CI) group. Eighty-one patients with CI were selected as the CI group, and 80 normal subjects over 50 years were selected as the control group. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, and malondialdehyde (MDA) content in serum were determined by colorimetric assays. Phosphorylation of GSK-3β was measured by enzyme-linked immunosorbent assay.

Results: (1) Compared with the control group, the SOD and GSH-Px activities in the DM group and DM + CI group were decreased, accompanied by higher MDA content. Furthermore, phosphorylation of GSK-3β was decreased. (2) In the DM + CI group, SOD activity was decreased on days 7 and 10 and month 3 compared to the CI group and was decreased on day 7 compared to the DM group. MDA content was increased from day 0 to month 3 compared to the CI group. On days 1, 7, and 10, GSH-Px activity was lower than the DM group, and on day 10 and month 3, it was lower than the CI group. Phosphorylation of GSK-3β was decreased on days 7 and 10 compared to the DM group and was decreased from day 1 to month 3 compared to the CI group.

Conclusion: In the present study, we demonstrated that the oxidative stress in peripheral lymphocytes of DM patients complicated with CI was stronger, and the GSK-3 activity was higher. It suggested that oxidative stress might enhance the GSK-3 activity, which might provide a diagnostic and therapeutic approach for DM complicated with CI, and targeting GSK-3 is a promising therapeutic target for the treatment of type 2 diabetes and its complications.