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Title: Decreased expression of orexin 1 receptor in adult mice testes during alloxan-induced diabetes mellitus perturbs testicular steroidogenesis and glucose homeostasis

Abstract

Diabetes mellitus (DM) affects male reproductive system and causes infertility. The male reproductive health is largely dependent upon uptake and proper utilization of glucose by testicular cells. Results show involvement of orexin A (OXA) and its receptor (OX1R) in regulation of steroidogenesis and glucose homeostasis in adult mice testis. However, the role of OX1R in regulation of testicular functions during hyperglycemia has not been investigated so far. The present study, therefore, examined the role of OX1R in regulation of steroidogenesis and glucose homeostasis in testis of adult mice during alloxan-induced type 1 DM. A significant decrease was noted in body weight and testis weight in alloxan-treated mice compared to controls. The blood glucose level, however, was markedly increased in treated animals than in controls. Further, serum and intratesticular level of testosterone, activities of testicular steroidogenic enzymes, and expressions of various steroidogenic markers, OX1R, glucose transporter 3 (GLUT3) and Wilms' tumor gene (WT1) were downregulated in treated mice. The level of glucose, activity of lactate dehydrogenase (LDH) and lactate concentration in the testes of diabetic mice were also decreased; a significant increase in the number of testicular apoptotic cells with concomitant increase in the expression of caspase-3 was noted in thesemore » mice. Furthermore, DM affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA). Results thus suggest that type 1 DM impairs testicular steroidogenesis and glucose homeostasis through inhibition of OXA/OX1R signaling cascade due to decreased OX1R expression in adult mice, thereby affecting germ cell survival and their proliferation in the testis. - Highlights: • Alloxan monohydrate treatment reduces expression of testicular OX1R in adult mice. • Decreased expression of OX1R perturbs testicular steroidogenesis. • Reduced expression of OX1R affects testicular glucose homeostasis. • Impairment in OX1R expression disturbs germ cell survival and proliferation.« less

Authors:
; ;
Publication Date:
OSTI Identifier:
22719064
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 490; Journal Issue: 4; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALLOXAN; BLOOD; DIABETES MELLITUS; GERM CELLS; GLUCOSE; HOMEOSTASIS; LACTATE DEHYDROGENASE; LACTATES; MICE; RECEPTORS; TESTES; TESTOSTERONE

Citation Formats

Joshi, Deepanshu, Sarkar, Debarshi, and Singh, Shio Kumar, E-mail: shioks53@gmail.com. Decreased expression of orexin 1 receptor in adult mice testes during alloxan-induced diabetes mellitus perturbs testicular steroidogenesis and glucose homeostasis. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.07.026.
Joshi, Deepanshu, Sarkar, Debarshi, & Singh, Shio Kumar, E-mail: shioks53@gmail.com. Decreased expression of orexin 1 receptor in adult mice testes during alloxan-induced diabetes mellitus perturbs testicular steroidogenesis and glucose homeostasis. United States. doi:10.1016/J.BBRC.2017.07.026.
Joshi, Deepanshu, Sarkar, Debarshi, and Singh, Shio Kumar, E-mail: shioks53@gmail.com. Sat . "Decreased expression of orexin 1 receptor in adult mice testes during alloxan-induced diabetes mellitus perturbs testicular steroidogenesis and glucose homeostasis". United States. doi:10.1016/J.BBRC.2017.07.026.
@article{osti_22719064,
title = {Decreased expression of orexin 1 receptor in adult mice testes during alloxan-induced diabetes mellitus perturbs testicular steroidogenesis and glucose homeostasis},
author = {Joshi, Deepanshu and Sarkar, Debarshi and Singh, Shio Kumar, E-mail: shioks53@gmail.com},
abstractNote = {Diabetes mellitus (DM) affects male reproductive system and causes infertility. The male reproductive health is largely dependent upon uptake and proper utilization of glucose by testicular cells. Results show involvement of orexin A (OXA) and its receptor (OX1R) in regulation of steroidogenesis and glucose homeostasis in adult mice testis. However, the role of OX1R in regulation of testicular functions during hyperglycemia has not been investigated so far. The present study, therefore, examined the role of OX1R in regulation of steroidogenesis and glucose homeostasis in testis of adult mice during alloxan-induced type 1 DM. A significant decrease was noted in body weight and testis weight in alloxan-treated mice compared to controls. The blood glucose level, however, was markedly increased in treated animals than in controls. Further, serum and intratesticular level of testosterone, activities of testicular steroidogenic enzymes, and expressions of various steroidogenic markers, OX1R, glucose transporter 3 (GLUT3) and Wilms' tumor gene (WT1) were downregulated in treated mice. The level of glucose, activity of lactate dehydrogenase (LDH) and lactate concentration in the testes of diabetic mice were also decreased; a significant increase in the number of testicular apoptotic cells with concomitant increase in the expression of caspase-3 was noted in these mice. Furthermore, DM affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA). Results thus suggest that type 1 DM impairs testicular steroidogenesis and glucose homeostasis through inhibition of OXA/OX1R signaling cascade due to decreased OX1R expression in adult mice, thereby affecting germ cell survival and their proliferation in the testis. - Highlights: • Alloxan monohydrate treatment reduces expression of testicular OX1R in adult mice. • Decreased expression of OX1R perturbs testicular steroidogenesis. • Reduced expression of OX1R affects testicular glucose homeostasis. • Impairment in OX1R expression disturbs germ cell survival and proliferation.},
doi = {10.1016/J.BBRC.2017.07.026},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 490,
place = {United States},
year = {2017},
month = {9}
}