title: Zinc deficiency exacerbates diabetic down-regulation of Akt expression and function in the testis: essential roles of PTEN, PTP1B and TRB3.
abstract: Since zinc (Zn) plays an important role in the spermatogenesis and Zn deficiency exacerbated diabetes-induced testicular apoptosis, the present study investigated the effect of Zn deficiency on diabetes-induced testicular Akt-mediated glucose metabolism changes and inflammation. Zn deficiency was induced by chronic treatment of normal and diabetic mice with the Zn chelator N,N,N',N', tetrakis (2-pyridylmethyl) ethylenediaminepentaethylene (TPEN). After diabetes onset induced by streptozotocin, both diabetic and age-matched control mice were given TPEN intraperitoneally for 4 months. Western blotting assay revealed that Akt-mediated glucose metabolism signaling was down-regulated in the diabetic testis and was further decreased in diabetic mice with Zn deficiency, reflected by reduced phosphorylation of both Akt and GSK-3β and increased phosphorylation of glycogen synthase along with a disarrangement of fatty acid metabolism (increased expression of PPAR-α and decreased adenosine-monophosphate-activated protein kinase phosphorylation). Testicular expressions of plasminogen activator inhibitor-1 and intracellular adhesion molecule-1 as inflammatory factors were increased in the TPEN or diabetes-alone group, but not additive in the group of diabetes with Zn deficiency. A mechanistic study showed that Akt negative regulators phosphatase and tensin homology deleted on chromosome 10 (PTEN), protein tyrosine phosphatases 1B and Tribbles 3 all increased in diabetic testis and further increased in the testis of diabetic mice with Zn deficiency. These studies suggest that Zn deficiency significantly exacerbated diabetic down-regulation of Akt expression and function, most likely by up-regulation of Akt negative regulators. Therefore, prevention of Zn deficiency for diabetic patients is important in order to avoid the exacerbation of diabetic inhibition of glucose metabolism in the testis.
authors: The Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors: Yuguang
authors: Y
authors: Zhao
authors: Yi
authors: Y
authors: Tan
authors: Junying
authors: J
authors: Dai
authors: Bo
authors: B
authors: Wang
authors: Bing
authors: B
authors: Li
authors: Luping
authors: L
authors: Guo
authors: Jiuwei
authors: J
authors: Cui
authors: Guanjun
authors: G
authors: Wang
authors: Wei
authors: W
authors: Li
authors: Lu
authors: L
authors: Cai
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental; D015536:Down-Regulation; D005029:Ethylenediamines / Q000494:pharmacology; D008297:Male; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*; D015032:Zinc / Q000172:deficiency
chemical_list: D018797:Cell Cycle Proteins; D005029:Ethylenediamines; C474830:TRB3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine