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Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis
BACKGROUND: Type 2 diabetes touches young subjects of reproductive age in epidemic proportion. This study assesses glucose, total InsulinT, Insulin2 and insulin receptor subunits α and β in testis during mouse development then, in the spontaneously type 2 diabetes models associated with infertility...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079543/ https://www.ncbi.nlm.nih.gov/pubmed/32183843 http://dx.doi.org/10.1186/s12958-020-00583-2 |
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author | Pelletier, R.-Marc Layeghkhavidaki, Hamed Vitale, María L. |
author_facet | Pelletier, R.-Marc Layeghkhavidaki, Hamed Vitale, María L. |
author_sort | Pelletier, R.-Marc |
collection | PubMed |
description | BACKGROUND: Type 2 diabetes touches young subjects of reproductive age in epidemic proportion. This study assesses glucose, total InsulinT, Insulin2 and insulin receptor subunits α and β in testis during mouse development then, in the spontaneously type 2 diabetes models associated with infertility db/db and ob/ob mice. IR-β and α were also assessed in spermatozoa (SPZ), anterior pituitary (AP) and serum. METHODS: Serum and tissue glucose were measured with enzymatic colorimetric assays and InsulinT and Insulin2 by ELISAs in serum, interstitial tissue- (ITf) and seminiferous tubule (STf) fractions in14- > 60-day-old normal and db/db, ob/ob and wild type (WT) mice. IR subunits were assessed by immunoblotting in tissues and by immunoprecipitation followed by immunoblotting in serum. RESULTS: Development: Glucose increased in serum, ITf and STf. InsulinT and Insulin2 dropped in serum; both were higher in STf than in ITf. In > 60-day-old mouse ITf, insulinT rose whereas Insulin2 decreased; InsulinT and Insulin2 rose concurrently in STf. Glucose and insulin were high in > 60-day-old ITf; in STf high insulin2 accompanied low glucose. One hundred ten kDa IR-β peaked in 28-day-old ITf and 14-day-old STf. One hundred thirty five kDa IR-α was high in ITf but decreased in STf. Glucose escalated in db/db and ob/ob sera. Glucose doubled in ITf while being halved in STf in db/db mice. Glucose significantly dropped in db/db and ob/ob mice spermatozoa. InsulinT and Insulin2 rose significantly in the serum, ITf and STf in db/db and ob/ob mice. One hundred ten kDa IR-β and 135 kDa IR-α decreased in db/db and ob/ob ITf. Only 110 kDa IR-β dropped in db/db and ob/ob STf and AP. One hundred ten kDa IR-β fell in db/db and ob/ob SPZ. One hundred ten kDa sIR-α rose in the db/db and ob/ob mouse sera. CONCLUSION: Insulin regulates glucose in tubules not in the interstitium. The mouse interstitium contains InsulinT and Insulin2 whereas tubules contain Insulin2. Decreased 110 kDa IR-β and 135 kDa IR-α in the db/db and ob/ob interstitial tissue suggest a loss of active receptor sites that could alter the testicular cell insulin binding and response to the hormone. Decreased IR-β levels were insufficient to stimulate downstream effectors in AP and tubules. IR-α shedding increased in db/db and ob/ob mice. |
format | Online Article Text |
id | pubmed-7079543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-70795432020-03-23 Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis Pelletier, R.-Marc Layeghkhavidaki, Hamed Vitale, María L. Reprod Biol Endocrinol Research BACKGROUND: Type 2 diabetes touches young subjects of reproductive age in epidemic proportion. This study assesses glucose, total InsulinT, Insulin2 and insulin receptor subunits α and β in testis during mouse development then, in the spontaneously type 2 diabetes models associated with infertility db/db and ob/ob mice. IR-β and α were also assessed in spermatozoa (SPZ), anterior pituitary (AP) and serum. METHODS: Serum and tissue glucose were measured with enzymatic colorimetric assays and InsulinT and Insulin2 by ELISAs in serum, interstitial tissue- (ITf) and seminiferous tubule (STf) fractions in14- > 60-day-old normal and db/db, ob/ob and wild type (WT) mice. IR subunits were assessed by immunoblotting in tissues and by immunoprecipitation followed by immunoblotting in serum. RESULTS: Development: Glucose increased in serum, ITf and STf. InsulinT and Insulin2 dropped in serum; both were higher in STf than in ITf. In > 60-day-old mouse ITf, insulinT rose whereas Insulin2 decreased; InsulinT and Insulin2 rose concurrently in STf. Glucose and insulin were high in > 60-day-old ITf; in STf high insulin2 accompanied low glucose. One hundred ten kDa IR-β peaked in 28-day-old ITf and 14-day-old STf. One hundred thirty five kDa IR-α was high in ITf but decreased in STf. Glucose escalated in db/db and ob/ob sera. Glucose doubled in ITf while being halved in STf in db/db mice. Glucose significantly dropped in db/db and ob/ob mice spermatozoa. InsulinT and Insulin2 rose significantly in the serum, ITf and STf in db/db and ob/ob mice. One hundred ten kDa IR-β and 135 kDa IR-α decreased in db/db and ob/ob ITf. Only 110 kDa IR-β dropped in db/db and ob/ob STf and AP. One hundred ten kDa IR-β fell in db/db and ob/ob SPZ. One hundred ten kDa sIR-α rose in the db/db and ob/ob mouse sera. CONCLUSION: Insulin regulates glucose in tubules not in the interstitium. The mouse interstitium contains InsulinT and Insulin2 whereas tubules contain Insulin2. Decreased 110 kDa IR-β and 135 kDa IR-α in the db/db and ob/ob interstitial tissue suggest a loss of active receptor sites that could alter the testicular cell insulin binding and response to the hormone. Decreased IR-β levels were insufficient to stimulate downstream effectors in AP and tubules. IR-α shedding increased in db/db and ob/ob mice. BioMed Central 2020-03-17 /pmc/articles/PMC7079543/ /pubmed/32183843 http://dx.doi.org/10.1186/s12958-020-00583-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Pelletier, R.-Marc Layeghkhavidaki, Hamed Vitale, María L. Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis |
title | Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis |
title_full | Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis |
title_fullStr | Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis |
title_full_unstemmed | Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis |
title_short | Glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis |
title_sort | glucose, insulin, insulin receptor subunits α and β in normal and spontaneously diabetic and obese ob/ob and db/db infertile mouse testis and hypophysis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079543/ https://www.ncbi.nlm.nih.gov/pubmed/32183843 http://dx.doi.org/10.1186/s12958-020-00583-2 |
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