Nigella sativa influences GLUT4 through the AMPK pathway

Type 2 diabetes is a global epidemic. Increasing evidence shows that estrogen has protective effects on insulin sensitivity. Decreased estrogen levels affect adipocytes response to insulin leading to increased circulating glucose levels and insulin resistance. AMP-activated protein kinase (AMPK) regulates cellular energy balance due to its role in glucose, lipid, and protein metabolism. Activation of AMPK results in translocation of glucose transporter 4 (GLUT4) to the plasma membrane which mobilizes glucose into the cell. The seed extract of Nigella sativa (NS) reduces elevated glucose levels. However, the molecular mechanisms involved in regulating glucose transport by NS remain elusive. We used an estrogen deficient animal model to examine whether NS and its active ingredient thymoquinone (TQ) modulate proteins involved in regulating glucose transport: AMPK, Akt, phosphorylated AMPK and Akt, and GLUT4.Sprague Dawley rats were either sham-operated or ovariectomized and divided into control, NS and TQ fed groups. Rats were fed the respective diets for 4 months and sacrificed. The peritoneal adipose tissue was collected and proteins were analyzed. NS fed sham-operated rats showed significant increase in AMPK phosphorylation, compared to control sham-operated rats. Similarly, ovariectomized rats fed TQ showed an increase in AMPK phosphorylation, compared to TQ sham-operated rats. Moreover, rats fed NS or TQ showed an increase in GLUT4 protein content, compared to the respective control groups. However, NS and TQ did not activate Akt phosphorylation