Table 3.
Minerals alter PI3K/Akt and/or GSK3 activities
| Minerals | Model system | Observed effects | Ref. |
|---|---|---|---|
| High levels in the body | |||
| Sodium, chloride, potassium | Monkey kidney cells, HeLa cells, human or mouse melanoma, mouse renal distal convoluted tubule cells, aWnk4+/+ and Wnk4D561A/+ mice, male SD rats. | High salt foods (mainly NaCl) cause potential hyperosmotic stress, which modulates PI3K/Akt/GSK3 activities; increase or decrease phosphorylation of NaCl transporter, regulated via insulin/PI3K pathway by low salt diet or high salt diet; high salt food causes early insulin resistance, stage 0 of the kinase insensitivity (Table 1). | [24, 49–52, 108, 109] |
| Calcium | Mouse osteoblast, human thyroid cancer cells, mouse neural crest cells. | Exert effects on PI3K/Akt and/or GSK3 pathway. | [47, 48, 110] |
| Manganese sulfate | Mouse macrophages. | Anti-inflammation via PI3K/Akt. | [111] |
| Magnesium sulfate | Rats with intestinal ischemia-reperfusion injury. | Protect injury via PI3K/Akt. | [58] |
| Fucosylated chondroitin sulfate | T2D mice. | Improve insulin sensitivity via activation of PI3K/Akt. | [59] |
| Heparan sulfate | Human normal astrocytes, and malignant gliomas, human breast cancer cells, human umbilical vein endothelial cells, wild type and Syndecan-1−/− mice infected by influenza. | Increase/Reduce PI3K/Akt/ERK signaling, carcinogenesis/anti-cancer and anti-inflammation. | [112–115] |
| Magnesium | Brains of Wistar rats, patients with diabetes. | Required for GSK3 activation; EDTA Chelation Therapy decreases CVD events in patients with diabetes. | [116, 117] |
| Trace levels in the body | Wistar rats, mouse hepatocytes. | Induce injury regulates PI3K/Akt/GSK3β pathway, whereas aged rats have less sensitivity of the regulation; iron oxide nanoparticles-mediated cytotoxicity related to PI3K/Akt pathway. | [118, 119] |
| Iron | |||
| Zinc or copper | Mouse myogenic cells, monkey kidney cells, mouse embryonic fibroblast, human hepatoma cells, human neuroblastoma cells, human prostate epithelial cells. | Stimulates PI3K/Akt signaling, leading to inhibition of GSK3β; zinc deficiency adds Akt signaling. | [120–124] |
| Iodine | SD rats. | Required for synthesis of thyroid hormones that activates Akt. | [22] |
| Manganese | Mouse microglial cells, human lung epithelial cells. | Induce inducible nitric oxide synthase expression via activation of both MAP kinase and PI3K/Akt pathways; increase the expression of prostaglandin-endoperoxide synthase 2 (COX-2) via p38 and PI3K/Akt. | [125, 126] |
| Zinc and manganese | South Hampshire and Merinob CLN6 sheep. | Increased in the model with reduced expression of ceroid-lipofuscinosis neuronal protein 6, accompanying with activation of Akt/GSK3 signaling (stage 1 of the kinase insensitivity (Table I)), and neurodegeneration. | [127] |
| Selenium | Human prostate cancer cells. | Reduce the activities of PI3K/Akt. | [128] |
| Aluminum fluoride | Mouse adipose cells. | Induce G-protein-linked PI3K signaling. | [129] |
| Fluorine | SD rats. | Accumulation of it relates to increase of PI3K/Akt and p38 and tissue in bone tissue of fluorosis rats. | [130] |
| Chromium | Mouse myoblast cells. | Increase expression glucose transporter and insulin receptor, resulting in enhanced glucose uptake. | [131] |
a WNK with-no-lysine kinase,b CLN ceroid-lipofuscinosis neuronal protein