Male hypogonadism induced by high fat diet and low dose streptozotocin is mediated by activated endoplasmic reticulum stress and IκBβ and attenuated by argirein and valsartan.

Abstract

Male hypogonadism is frequently accompanied with type 2 diabetes due to testicular dysfunction, but the origin of the pathogenesis is not known. We measured whether pro-inflammatory factors including endoplasmic reticulum (ER) stress chaperones and inhibitory κBβ (IκBβ) contribute to testis damage in type 2 diabetic rats produced by a high-fat diet (HFD) and low dose streptozotocin (STZ). We determined whether these can be attenuated by the anti-inflammatory activity of argirein a derivative of rhein as compared to valsartan. Reduced testosterone and LH (luteinizing hormone) levels in serum were significant in association with a decrease in the levels of mRNA and steroidogenic acute regulatory protein (StAR), insulin receptor substrate (IRS-1), activated IκBβ and ER stress chaperone C/EBP homologous protein (CHOP) in the diabetic testis and sperm count, motility and sexual behaviors were reduced in vivo. Additionally, Leydig cells cultured with high glucose showed upregulated IκBβ, ER stress sensor PERK (PKR-like ER kinase) and p-Akt/Akt in vitro. These changes may be due to a component of inflammation linked to activated NADPH oxidase and were significantly alleviated by either argirein or valsartan. In conclusion, diabetic testopathy induced by a HFD and low STZ is characterized by an entity of inflammation and is alleviated by argirein and valsartan through normalizing activated IκBβ and ER stress.

• Authors: Gui-Lai Liu, Yu-Mao Zhang, De-Zai Dai, Ming-Jian Ding, Xiao-Dong Cong, Yin Dai
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 713 Issue 1-3 Pg. 78-88 (Aug 05 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 23665494 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Anthraquinones
• Anti-Inflammatory Agents
• Drug Combinations
• I kappa B beta protein
• I-kappa B Proteins
• Tetrazoles
• argirein
• Streptozocin
• Valsartan
• Arginine
• Valine

Topics

• Animals
• Anthraquinones (administration & dosage, therapeutic use)
• Anti-Inflammatory Agents (administration & dosage, therapeutic use)
• Arginine (administration & dosage, therapeutic use)
• Diabetes Mellitus, Experimental (complications, immunology, metabolism)
• Diabetes Mellitus, Type 2 (complications, immunology, metabolism)
• Diet, High-Fat (adverse effects)
• Drug Combinations
• Endoplasmic Reticulum Stress (drug effects)
• Hypogonadism (etiology, immunology, metabolism, prevention & control)
• I-kappa B Proteins (metabolism)
• Male
• Rats
• Rats, Sprague-Dawley
• Sexual Behavior, Animal (drug effects)
• Streptozocin (pharmacology)
• Tetrazoles (administration & dosage, therapeutic use)
• Valine (administration & dosage, analogs & derivatives, therapeutic use)
• Valsartan