Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice.
Glucose sensing (eg. glucokinase activity) becomes impaired in the development of type 2 diabetes, the etiology of which is unclear. Estrogen can stimulate glucokinase activity, whereas the pervasive environmental pollutant bisphenol A (BPA) can inhibit estrogen action, hence we aimed to determine t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3726717?pdf=render |
| _version_ | 1818538598007308288 |
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| author | Leigh Perreault Carrie McCurdy Anna A Kerege Julie Houck Kristine Færch Bryan C Bergman |
| author_facet | Leigh Perreault Carrie McCurdy Anna A Kerege Julie Houck Kristine Færch Bryan C Bergman |
| author_sort | Leigh Perreault |
| collection | DOAJ |
| description | Glucose sensing (eg. glucokinase activity) becomes impaired in the development of type 2 diabetes, the etiology of which is unclear. Estrogen can stimulate glucokinase activity, whereas the pervasive environmental pollutant bisphenol A (BPA) can inhibit estrogen action, hence we aimed to determine the effect of BPA on glucokinase activity directly.To evaluate a potential acute effect on hepatic glucokinase activity, BPA in water (n = 5) vs. water alone (n = 5) was administered at the EPA's purported "safe dose" (50 µg/kg) by gavage to lean 6-month old male C57BL/6 mice. Two hours later, animals were euthanized and hepatic glucokinase activity measured over glucose levels from 1-20 mmol/l in liver homogenate. To determine the effect of chronic BPA exposure on hepatic glucokinase activity, lean 6-month old male C57BL/6 mice were provided with water (n = 15) or water with 1.75 mM BPA (∼50 µg/kg/day; n = 14) for 2 weeks. Following the 2-week exposure, animals were euthanized and glucokinase activity measured as above.Hepatic glucokinase activity was signficantly suppressed after 2 hours in animals given an oral BPA bolus compared to those who received only water (p = 0.002-0.029 at glucose 5-20 mmol/l; overall treatment effect p<0.001). Exposure to BPA over 2 weeks also suppressed hepatic glucokinase activity in exposed vs. unexposed mice (overall treatment effect, p = 0.003). In both experiments, the Hill coefficient was higher and Vmax lower in mice treated with BPA.Both acute and chronic exposure to BPA significantly impair hepatic glucokinase activity and function. These findings identify a potential mechanism for how BPA may increase risk for diabetes. |
| first_indexed | 2024-12-11T21:31:01Z |
| format | Article |
| id | doaj.art-19df93e66d4645c9ab6636d724743be0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T21:31:01Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-19df93e66d4645c9ab6636d724743be02022-12-22T00:50:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6999110.1371/journal.pone.0069991Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice.Leigh PerreaultCarrie McCurdyAnna A KeregeJulie HouckKristine FærchBryan C BergmanGlucose sensing (eg. glucokinase activity) becomes impaired in the development of type 2 diabetes, the etiology of which is unclear. Estrogen can stimulate glucokinase activity, whereas the pervasive environmental pollutant bisphenol A (BPA) can inhibit estrogen action, hence we aimed to determine the effect of BPA on glucokinase activity directly.To evaluate a potential acute effect on hepatic glucokinase activity, BPA in water (n = 5) vs. water alone (n = 5) was administered at the EPA's purported "safe dose" (50 µg/kg) by gavage to lean 6-month old male C57BL/6 mice. Two hours later, animals were euthanized and hepatic glucokinase activity measured over glucose levels from 1-20 mmol/l in liver homogenate. To determine the effect of chronic BPA exposure on hepatic glucokinase activity, lean 6-month old male C57BL/6 mice were provided with water (n = 15) or water with 1.75 mM BPA (∼50 µg/kg/day; n = 14) for 2 weeks. Following the 2-week exposure, animals were euthanized and glucokinase activity measured as above.Hepatic glucokinase activity was signficantly suppressed after 2 hours in animals given an oral BPA bolus compared to those who received only water (p = 0.002-0.029 at glucose 5-20 mmol/l; overall treatment effect p<0.001). Exposure to BPA over 2 weeks also suppressed hepatic glucokinase activity in exposed vs. unexposed mice (overall treatment effect, p = 0.003). In both experiments, the Hill coefficient was higher and Vmax lower in mice treated with BPA.Both acute and chronic exposure to BPA significantly impair hepatic glucokinase activity and function. These findings identify a potential mechanism for how BPA may increase risk for diabetes.http://europepmc.org/articles/PMC3726717?pdf=render |
| spellingShingle | Leigh Perreault Carrie McCurdy Anna A Kerege Julie Houck Kristine Færch Bryan C Bergman Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice. PLoS ONE |
| title | Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice. |
| title_full | Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice. |
| title_fullStr | Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice. |
| title_full_unstemmed | Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice. |
| title_short | Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice. |
| title_sort | bisphenol a impairs hepatic glucose sensing in c57bl 6 male mice |
| url | http://europepmc.org/articles/PMC3726717?pdf=render |
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