Journal of Basic and Clinical Pathophysiology

Journal of Basic and Clinical Pathophysiology

Down-regulation of insulin substrate receptor 1 and 2 in the liver may be a mechanism for insulin resistance during testosterone deprivation

Document Type : Research Paper

Authors
Mahnaz Ghowsi
Sajjad Sisakhtnezhad
Department of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran
10.22070/jbcp.2021.14471.1142
Abstract
Background and Objective: Type 2 diabetes is a global concern worldwide. Despite extensive studies on the physiological effects of diabetes on the testicular functions, the impact of testosterone deficiency on the glucose homeostasis remains to be clarified. This study was designed to investigate the effects of testosterone deprivation and its replacement with testosterone enanthate on the molecular mechanisms of insulin signaling pathway in the liver of rats.
Materials and Methods: We first established a rat model of testosterone deficiency by castration (CAS-S). Subsequently, the castrated rats were administrated by subcutaneous injection of testosterone (CAS-T). Thereafter, fasting blood glucose (FBG), insulin, and homeostasis model-insulin resistance (HOMA-IR) level was assessed. The testosterone and insulin levels were further analyzed by ELISA. The mRNA expression of insulin receptor (IR)-β, insulin receptor-substrate (IRS)1 and 2 as well as glucose transporter (GLUT) 2 in the liver was analyzed by q-RT-PCR assay.
Results: Our data showed that testosterone deprivation significantly increases FBG and HOMA-IR and down-regulates IRS-1 and IRS-2 mRNA expression in the liver. However, the mRNA expression of GLUT2 and IR-β was not affected. We also found that testosterone administration could improve the liver insulin resistance.
Conclusion: These findings suggested that testosterone deprivation can impact insulin signaling in the liver via suppressing expression of IRS-1 and IRS-2 mRNA and treatment with testosterone can improve the insulin resistance in the castrated rats. Further experimental and clinical pathways are needed to be assessed for clinical application of our finding.
Keywords
Androgen
Hepatic insulin resistance
Diabetes
IRS 1 and 2
Glucose transporter 2
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Journal of Basic and Clinical Pathophysiology
Volume 9, Issue 1
May 2021
Pages 23-40