Chromium Mitigates the Iron-Induced Glucose Metabolism Disorder via the PI3K/Akt/Bcl-2 Signaling Pathway: An In Vivo...

Numerous studies have focused on the independent effects of iron and chromium on type 2 diabetes mellitus (T2DM); however, studies on their combined effects remain limited. Therefore, we examined the combined effects of chromium and iron on glucose metabolism using an in vivo Wistar rat model. Male Wistar rats (N = 30) were divided into five groups: control (Ctr), iron excess (IE), and three chromium-treated groups receiving low, medium, or high doses of chromium picolinate (IEC1-3). Rats were fed diets with adequate or excess iron (as iron citrate) and varying doses of chromium for 8 weeks. Glucose metabolism, oxidative stress markers, histopathology of pancreatic tissue, and PI3K/Akt/Bcl-2-related gene and protein expression in pancreatic tissue were evaluated. We observed a significant increase in fasting blood glucose (FBG) and insulin resistance in the IE group. Iron excess increased serum malondialdehyde (MDA), reduced superoxide dismutase (SOD) activity, downregulated phosphorylation of phosphatidylinositol 3-kinase (p-PI3K), phospho-protein kinase B (p-Akt) proteins, and B-cell lymphoma 2 (Bcl-2), and upregulated Bax and cleaved caspase-9 in pancreatic tissue, leading to pancreatic β-cell apoptosis. In contrast, chromium supplementation reversed these effects, improving pancreatic β-cell apoptosis and glucose metabolism. Our findings suggest that chromium may attenuate iron-induced pancreatic β-cell apoptosis and glucose metabolism impairment, potentially by reducing oxidative damage and modulating the PI3K/Akt/Bcl-2 signaling pathway. These results highlight a potentially protective role of chromium in the context of iron excess, which could inform future research into nutritional interventions for metabolic disorders. Further studies are warranted to fully elucidate the underlying mechanisms and translational applicability.