Improved glucose handling in female rat offspring of a hypertensive pregnancy with intrauterine growth restriction
Abstract Hypertensive disorders of pregnancy, intrauterine growth restriction (IUGR), and reduced pancreatic β‐cell area increases risk of offspring developing type 2 diabetes (T2D). Our previous studies using rat reduced uteroplacental perfusion pressure (RUPP) model of gestational hypertension and...
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Wiley
2025-02-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.70222 |
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| author | Melissa A. Cedars Kate M. Root Brian Akhaphong Megan Beetch Abigail E. Miles Ronald R. Regal Emilyn U. Alejandro Jean F. Regal |
| author_facet | Melissa A. Cedars Kate M. Root Brian Akhaphong Megan Beetch Abigail E. Miles Ronald R. Regal Emilyn U. Alejandro Jean F. Regal |
| author_sort | Melissa A. Cedars |
| collection | DOAJ |
| description | Abstract Hypertensive disorders of pregnancy, intrauterine growth restriction (IUGR), and reduced pancreatic β‐cell area increases risk of offspring developing type 2 diabetes (T2D). Our previous studies using rat reduced uteroplacental perfusion pressure (RUPP) model of gestational hypertension and IUGR demonstrated reduced pancreatic β‐cell area in offspring at embryonic day 19 and postnatal day 13 (PD13). We hypothesized reduced β‐cell area early in life would manifest as hyperglycemia and glucose intolerance as animals aged. However, glucose intolerance did not differ in RUPP versus control offspring to 1 year of life, whether intraperitoneal or oral glucose challenge. At PD28, female RUPP offspring show normalized β‐cell area compared to controls and improved ability to clear glucose following oral challenge. Oral glucose challenge results in significant increase in incretin GLP‐1 in RUPP female offspring compared to control. Insulin tolerance did not differ amongst control and RUPP offspring, except at PD28 where insulin reduced blood glucose more effectively in RUPP female offspring versus control. Insulin‐induced vasodilation in isolated aorta and insulin signaling in fat are more pronounced in RUPP PD28 female offspring versus control. Thus, our studies demonstrate compensatory mechanisms protect IUGR offspring of a hypertensive pregnancy from long‐term metabolic effects and development of T2D. |
| format | Article |
| id | doaj-art-142d83c072234bf6aa2a9c904a44a7ca |
| institution | DOAJ |
| issn | 2051-817X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-142d83c072234bf6aa2a9c904a44a7ca2025-08-20T03:10:39ZengWileyPhysiological Reports2051-817X2025-02-01133n/an/a10.14814/phy2.70222Improved glucose handling in female rat offspring of a hypertensive pregnancy with intrauterine growth restrictionMelissa A. Cedars0Kate M. Root1Brian Akhaphong2Megan Beetch3Abigail E. Miles4Ronald R. Regal5Emilyn U. Alejandro6Jean F. Regal7Department of Biomedical Sciences University of Minnesota Medical School Duluth Minnesota USADepartment of Biomedical Sciences University of Minnesota Medical School Duluth Minnesota USADepartment of Integrative Biology and Physiology University of Minnesota Medical School Minneapolis Minnesota USADepartment of Integrative Biology and Physiology University of Minnesota Medical School Minneapolis Minnesota USADepartment of Biomedical Sciences University of Minnesota Medical School Duluth Minnesota USADepartment of Mathematics and Statistics University of Minnesota Duluth Minnesota USADepartment of Integrative Biology and Physiology University of Minnesota Medical School Minneapolis Minnesota USADepartment of Biomedical Sciences University of Minnesota Medical School Duluth Minnesota USAAbstract Hypertensive disorders of pregnancy, intrauterine growth restriction (IUGR), and reduced pancreatic β‐cell area increases risk of offspring developing type 2 diabetes (T2D). Our previous studies using rat reduced uteroplacental perfusion pressure (RUPP) model of gestational hypertension and IUGR demonstrated reduced pancreatic β‐cell area in offspring at embryonic day 19 and postnatal day 13 (PD13). We hypothesized reduced β‐cell area early in life would manifest as hyperglycemia and glucose intolerance as animals aged. However, glucose intolerance did not differ in RUPP versus control offspring to 1 year of life, whether intraperitoneal or oral glucose challenge. At PD28, female RUPP offspring show normalized β‐cell area compared to controls and improved ability to clear glucose following oral challenge. Oral glucose challenge results in significant increase in incretin GLP‐1 in RUPP female offspring compared to control. Insulin tolerance did not differ amongst control and RUPP offspring, except at PD28 where insulin reduced blood glucose more effectively in RUPP female offspring versus control. Insulin‐induced vasodilation in isolated aorta and insulin signaling in fat are more pronounced in RUPP PD28 female offspring versus control. Thus, our studies demonstrate compensatory mechanisms protect IUGR offspring of a hypertensive pregnancy from long‐term metabolic effects and development of T2D.https://doi.org/10.14814/phy2.70222Beta celldevelopmental programminggestational hypertensionglucose intoleranceincretinsintrauterine growth restriction |
| spellingShingle | Melissa A. Cedars Kate M. Root Brian Akhaphong Megan Beetch Abigail E. Miles Ronald R. Regal Emilyn U. Alejandro Jean F. Regal Improved glucose handling in female rat offspring of a hypertensive pregnancy with intrauterine growth restriction Physiological Reports Beta cell developmental programming gestational hypertension glucose intolerance incretins intrauterine growth restriction |
| title | Improved glucose handling in female rat offspring of a hypertensive pregnancy with intrauterine growth restriction |
| title_full | Improved glucose handling in female rat offspring of a hypertensive pregnancy with intrauterine growth restriction |
| title_fullStr | Improved glucose handling in female rat offspring of a hypertensive pregnancy with intrauterine growth restriction |
| title_full_unstemmed | Improved glucose handling in female rat offspring of a hypertensive pregnancy with intrauterine growth restriction |
| title_short | Improved glucose handling in female rat offspring of a hypertensive pregnancy with intrauterine growth restriction |
| title_sort | improved glucose handling in female rat offspring of a hypertensive pregnancy with intrauterine growth restriction |
| topic | Beta cell developmental programming gestational hypertension glucose intolerance incretins intrauterine growth restriction |
| url | https://doi.org/10.14814/phy2.70222 |
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