Sex-specific effect of P2Y2 purinergic receptor on glucose metabolism during acute inflammation

The sex of an animal impacts glucose sensitivity, but little information is available regarding the mechanisms causing that difference, especially during acute inflammation. We examined sex-specific differences in the role of the P2Y2 receptor (P2Y2R) in glucose flux with and without LPS challenge....

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Main Authors: Randi J. Ulbricht, Christian A. Rivas, Hailee Marino, Erin Snyder, Dana James, Jamila Makhloufi, Nathan Johnson, Scott Zimmerman, Jianjie Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-08-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1248139/full
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author Randi J. Ulbricht
Christian A. Rivas
Hailee Marino
Erin Snyder
Dana James
Jamila Makhloufi
Nathan Johnson
Scott Zimmerman
Jianjie Wang
author_facet Randi J. Ulbricht
Christian A. Rivas
Hailee Marino
Erin Snyder
Dana James
Jamila Makhloufi
Nathan Johnson
Scott Zimmerman
Jianjie Wang
author_sort Randi J. Ulbricht
collection DOAJ
description The sex of an animal impacts glucose sensitivity, but little information is available regarding the mechanisms causing that difference, especially during acute inflammation. We examined sex-specific differences in the role of the P2Y2 receptor (P2Y2R) in glucose flux with and without LPS challenge. Male and female wild-type and P2Y2R knockout mice (P2Y2R-/-) were injected with LPS or saline and glucose tolerance tests (GTT) were performed. P2Y2R, insulin receptor, and GLUT4 transporter gene expression was also evaluated. Female mice had reduced fasting plasma glucose and females had reduced glucose excursion times compared to male mice during GTT. P2Y2R-/- males had significantly decreased glucose flux throughout the GTT as compared to all female mice. Acute inflammation reduced fasting plasma glucose and the GTT area under the curve in both sexes. While both wild-type and P2Y2R-/- male animals displayed reduced fasting glucose in LPS treatment, female mice did not have significant difference in glucose tolerance, suggesting that the effects of P2Y2R are specific to male mice, even under inflammatory conditions. Overall, we conclude that the role for the purinergic receptor, P2Y2R, in regulating glucose metabolism is minimal in females but plays a large role in male mice, particularly in the acute inflammatory state.
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spelling doaj.art-dad484205cfa45f4b464dc0b7d0ec90e2023-08-28T15:09:53ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-08-011410.3389/fendo.2023.12481391248139Sex-specific effect of P2Y2 purinergic receptor on glucose metabolism during acute inflammationRandi J. UlbrichtChristian A. RivasHailee MarinoErin SnyderDana JamesJamila MakhloufiNathan JohnsonScott ZimmermanJianjie WangThe sex of an animal impacts glucose sensitivity, but little information is available regarding the mechanisms causing that difference, especially during acute inflammation. We examined sex-specific differences in the role of the P2Y2 receptor (P2Y2R) in glucose flux with and without LPS challenge. Male and female wild-type and P2Y2R knockout mice (P2Y2R-/-) were injected with LPS or saline and glucose tolerance tests (GTT) were performed. P2Y2R, insulin receptor, and GLUT4 transporter gene expression was also evaluated. Female mice had reduced fasting plasma glucose and females had reduced glucose excursion times compared to male mice during GTT. P2Y2R-/- males had significantly decreased glucose flux throughout the GTT as compared to all female mice. Acute inflammation reduced fasting plasma glucose and the GTT area under the curve in both sexes. While both wild-type and P2Y2R-/- male animals displayed reduced fasting glucose in LPS treatment, female mice did not have significant difference in glucose tolerance, suggesting that the effects of P2Y2R are specific to male mice, even under inflammatory conditions. Overall, we conclude that the role for the purinergic receptor, P2Y2R, in regulating glucose metabolism is minimal in females but plays a large role in male mice, particularly in the acute inflammatory state.https://www.frontiersin.org/articles/10.3389/fendo.2023.1248139/fullpurinergic signalingglucose homeostasisP2Y receptorinflammationsex-dependence
spellingShingle Randi J. Ulbricht
Christian A. Rivas
Hailee Marino
Erin Snyder
Dana James
Jamila Makhloufi
Nathan Johnson
Scott Zimmerman
Jianjie Wang
Sex-specific effect of P2Y2 purinergic receptor on glucose metabolism during acute inflammation
Frontiers in Endocrinology
purinergic signaling
glucose homeostasis
P2Y receptor
inflammation
sex-dependence
title Sex-specific effect of P2Y2 purinergic receptor on glucose metabolism during acute inflammation
title_full Sex-specific effect of P2Y2 purinergic receptor on glucose metabolism during acute inflammation
title_fullStr Sex-specific effect of P2Y2 purinergic receptor on glucose metabolism during acute inflammation
title_full_unstemmed Sex-specific effect of P2Y2 purinergic receptor on glucose metabolism during acute inflammation
title_short Sex-specific effect of P2Y2 purinergic receptor on glucose metabolism during acute inflammation
title_sort sex specific effect of p2y2 purinergic receptor on glucose metabolism during acute inflammation
topic purinergic signaling
glucose homeostasis
P2Y receptor
inflammation
sex-dependence
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1248139/full
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