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Table 3 Minerals alter PI3K/Akt and/or GSK3 activities

From: Chronic over-nutrition and dysregulation of GSK3 in diseases

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, 4952, 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. [112115]
 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]
 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. [120124]
 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]
  1. a WNK with-no-lysine kinase,b CLN ceroid-lipofuscinosis neuronal protein