Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy.
<h4>Purpose</h4>Female mice have been found to be resistant to streptozotocin (STZ)-induced diabetes, and pre-clinical research related to diabetic complications commonly omits females. The purpose of this study was to develop a method to induce diabetes in female mice, and to determine...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0238727 |
| _version_ | 1818400849029758976 |
|---|---|
| author | Aicha Saadane Emma M Lessieur Yunpeng Du Haitao Liu Timothy S Kern |
| author_facet | Aicha Saadane Emma M Lessieur Yunpeng Du Haitao Liu Timothy S Kern |
| author_sort | Aicha Saadane |
| collection | DOAJ |
| description | <h4>Purpose</h4>Female mice have been found to be resistant to streptozotocin (STZ)-induced diabetes, and pre-clinical research related to diabetic complications commonly omits females. The purpose of this study was to develop a method to induce diabetes in female mice, and to determine if retinas of diabetic female mice develop molecular changes and histopathological abnormalities comparable to those which develop in male diabetic mice.<h4>Methods</h4>To induce diabetes, animals of both sexes received daily intraperitoneal (i.p.) injection of STZ for 5 consecutive days at 55 mg/kg BW (a dose that is known to induce diabetes in male mice) or for females, 75 mg/kg BW of STZ. Retinal abnormalities that have been implicated in the development of the retinopathy (superoxide generation and expression of inflammatory proteins, iNOS and ICAM-1) were evaluated at 2 months of diabetes, and retinal capillary degeneration was evaluated at 8 months of diabetes.<h4>Results</h4>Daily i.p. injection of STZ for 5 consecutive days at a concentration of 55 mg/kg BW was sufficient to induce diabetes in 100% of male mice, but only 33% of female mice. However, females did become hyperglycemic when the dose of STZ administered was increased to 75 mg/kg BW. The resulting STZ-induced hyperglycemia in female and male mice was sustained for at least 8 months. After induction of the diabetes, both sexes responded similarly with respect to the oxidative stress, expression of iNOS, and degeneration of retinal capillaries, but differed in the limited population evaluated with respect to expression of ICAM-1.<h4>Conclusions</h4>The resistance of female mice to STZ-induced diabetes can be overcome by increasing the dose of STZ used. Female mice can, and should, be included in pre-clinical studies of diabetes and its complications. |
| first_indexed | 2024-12-14T07:43:06Z |
| format | Article |
| id | doaj.art-1a0d1aec47344c88ac9990711886ffcf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T07:43:06Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1a0d1aec47344c88ac9990711886ffcf2022-12-21T23:10:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01159e023872710.1371/journal.pone.0238727Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy.Aicha SaadaneEmma M LessieurYunpeng DuHaitao LiuTimothy S Kern<h4>Purpose</h4>Female mice have been found to be resistant to streptozotocin (STZ)-induced diabetes, and pre-clinical research related to diabetic complications commonly omits females. The purpose of this study was to develop a method to induce diabetes in female mice, and to determine if retinas of diabetic female mice develop molecular changes and histopathological abnormalities comparable to those which develop in male diabetic mice.<h4>Methods</h4>To induce diabetes, animals of both sexes received daily intraperitoneal (i.p.) injection of STZ for 5 consecutive days at 55 mg/kg BW (a dose that is known to induce diabetes in male mice) or for females, 75 mg/kg BW of STZ. Retinal abnormalities that have been implicated in the development of the retinopathy (superoxide generation and expression of inflammatory proteins, iNOS and ICAM-1) were evaluated at 2 months of diabetes, and retinal capillary degeneration was evaluated at 8 months of diabetes.<h4>Results</h4>Daily i.p. injection of STZ for 5 consecutive days at a concentration of 55 mg/kg BW was sufficient to induce diabetes in 100% of male mice, but only 33% of female mice. However, females did become hyperglycemic when the dose of STZ administered was increased to 75 mg/kg BW. The resulting STZ-induced hyperglycemia in female and male mice was sustained for at least 8 months. After induction of the diabetes, both sexes responded similarly with respect to the oxidative stress, expression of iNOS, and degeneration of retinal capillaries, but differed in the limited population evaluated with respect to expression of ICAM-1.<h4>Conclusions</h4>The resistance of female mice to STZ-induced diabetes can be overcome by increasing the dose of STZ used. Female mice can, and should, be included in pre-clinical studies of diabetes and its complications.https://doi.org/10.1371/journal.pone.0238727 |
| spellingShingle | Aicha Saadane Emma M Lessieur Yunpeng Du Haitao Liu Timothy S Kern Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy. PLoS ONE |
| title | Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy. |
| title_full | Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy. |
| title_fullStr | Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy. |
| title_full_unstemmed | Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy. |
| title_short | Successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy. |
| title_sort | successful induction of diabetes in mice demonstrates no gender difference in development of early diabetic retinopathy |
| url | https://doi.org/10.1371/journal.pone.0238727 |
| work_keys_str_mv | AT aichasaadane successfulinductionofdiabetesinmicedemonstratesnogenderdifferenceindevelopmentofearlydiabeticretinopathy AT emmamlessieur successfulinductionofdiabetesinmicedemonstratesnogenderdifferenceindevelopmentofearlydiabeticretinopathy AT yunpengdu successfulinductionofdiabetesinmicedemonstratesnogenderdifferenceindevelopmentofearlydiabeticretinopathy AT haitaoliu successfulinductionofdiabetesinmicedemonstratesnogenderdifferenceindevelopmentofearlydiabeticretinopathy AT timothyskern successfulinductionofdiabetesinmicedemonstratesnogenderdifferenceindevelopmentofearlydiabeticretinopathy |