| Zinc deficiency exacerbates diabetic down-regulation of Akt expression and function in the testis: essential roles of PTEN, PTP1B and TRB3. | |
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MedLine Citation:
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PMID: 22000581 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yuguang Zhao; Yi Tan; Junying Dai; Bo Wang; Bing Li; Luping Guo; Jiuwei Cui; Guanjun Wang; Wei Li; Lu Cai |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-12 |
Journal Detail:
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Title: The Journal of nutritional biochemistry Volume: - ISSN: 1873-4847 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9010081 Medline TA: J Nutr Biochem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Published by Elsevier Inc. |
Affiliation:
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The Cancer Center, the First Hospital of Jilin University, Changchun 130021, China; KCHRI, the Department of Pediatrics, University of Louisville, Louisville, KY 40292, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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