Zerumbone Ameliorates High Glucose-Induced Reduction in AMP-Activated Protein Kinase Phosphorylation in Tubular Kidney Cells

AMP-activated protein kinase (AMPK) plays an important role in pathophysiology of diabetes and its complications. In recent years, its role in kidney as a therapeutic target in ameliorating diabetic kidney damage is receiving renewed attention. Efforts on identifying AMPK modulators from dietary sources have gained prominence because of the tremendous potential it harbors. We therefore, examined the effect of a few bioactives on AMPK phosphorylation in kidney tubular cells. AMPK phosphorylation at Thr(172) was reduced (0.42 +/- 0.05-fold change compared to the control; p < 0.01 vs control) after treatment with high glucose (30 mM) for 48 h and restored by zerumbone (1.59 +/- 0.20; p < 0.01 vs high glucose) but not by other tested modulators. Zerumbone also increased the phosphorylation of downstream target of AMPK, the acetylCoA carboxylase (ACC) without affecting the mitochondrial membrane potential and ADP/ATP ratio. Thus, zerumbone could potentially be explored as a therapeutic agent in bringing about energy homeostasis in diabetes where high glucose suppresses the AMPK pathway.