Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model
Female New Zealand obese (NZO) mice are an established model of preconceptional (pc.) prediabetes that progresses as gestational diabetes mellitus (GDM) during gestation. It is known that NZO mice show improvement in insulin sensitivity and glucose-stimulated insulin secretion (GSIS) during gestatio...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/12/6693 |
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| author | Moritz Liebmann Melissa Asuaje Pfeifer Katharina Grupe Stephan Scherneck |
| author_facet | Moritz Liebmann Melissa Asuaje Pfeifer Katharina Grupe Stephan Scherneck |
| author_sort | Moritz Liebmann |
| collection | DOAJ |
| description | Female New Zealand obese (NZO) mice are an established model of preconceptional (pc.) prediabetes that progresses as gestational diabetes mellitus (GDM) during gestation. It is known that NZO mice show improvement in insulin sensitivity and glucose-stimulated insulin secretion (GSIS) during gestation in vivo. The latter is no longer detectable in ex vivo perifusion experiments in isolated islets of Langerhans, suggesting a modulation by extrapancreatic factors. Here, we demonstrated that plasma 17β-estradiol (E2) levels increased markedly in NZO mice during gestation. The aim of this work was to determine whether these increased E2 levels are responsible for the improvement in metabolism during gestation. To achieve this goal, we examined its effects in isolated islets and primary hepatocytes of both NZO and metabolically healthy NMRI mice. E2 increased GSIS in the islets of both strains significantly. Hepatic glucose production (HGP) failed to be decreased by insulin in NZO hepatocytes but was reduced by E2 in both strains. Hepatocytes of pregnant NZO mice showed significantly lower glucose uptake (HGU) compared with NMRI controls, whereby E2 stimulation diminished this difference. Hepatocytes of pregnant NZO showed reduced glycogen content, increased cyclic adenosine monophosphate (cAMP) levels, and reduced AKT activation. These differences were abolished after E2 stimulation. In conclusion, our data indicate that E2 stabilizes and prevents deterioration of the metabolic state of the prediabetic NZO mice. E2 particularly increases GSIS and improves hepatic glucose utilization to a lower extent. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:33:36Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e4435eceb57040e8a05d68b39f7be4c42023-11-23T17:05:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312669310.3390/ijms23126693Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse ModelMoritz Liebmann0Melissa Asuaje Pfeifer1Katharina Grupe2Stephan Scherneck3Institute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Mendelssohnstraße 1, D-38106 Braunschweig, GermanyInstitute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Mendelssohnstraße 1, D-38106 Braunschweig, GermanyInstitute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Mendelssohnstraße 1, D-38106 Braunschweig, GermanyInstitute of Pharmacology, Toxicology and Clinical Pharmacy, Technische Universität Braunschweig, Mendelssohnstraße 1, D-38106 Braunschweig, GermanyFemale New Zealand obese (NZO) mice are an established model of preconceptional (pc.) prediabetes that progresses as gestational diabetes mellitus (GDM) during gestation. It is known that NZO mice show improvement in insulin sensitivity and glucose-stimulated insulin secretion (GSIS) during gestation in vivo. The latter is no longer detectable in ex vivo perifusion experiments in isolated islets of Langerhans, suggesting a modulation by extrapancreatic factors. Here, we demonstrated that plasma 17β-estradiol (E2) levels increased markedly in NZO mice during gestation. The aim of this work was to determine whether these increased E2 levels are responsible for the improvement in metabolism during gestation. To achieve this goal, we examined its effects in isolated islets and primary hepatocytes of both NZO and metabolically healthy NMRI mice. E2 increased GSIS in the islets of both strains significantly. Hepatic glucose production (HGP) failed to be decreased by insulin in NZO hepatocytes but was reduced by E2 in both strains. Hepatocytes of pregnant NZO mice showed significantly lower glucose uptake (HGU) compared with NMRI controls, whereby E2 stimulation diminished this difference. Hepatocytes of pregnant NZO showed reduced glycogen content, increased cyclic adenosine monophosphate (cAMP) levels, and reduced AKT activation. These differences were abolished after E2 stimulation. In conclusion, our data indicate that E2 stabilizes and prevents deterioration of the metabolic state of the prediabetic NZO mice. E2 particularly increases GSIS and improves hepatic glucose utilization to a lower extent.https://www.mdpi.com/1422-0067/23/12/6693estradiolprediabetesgestational diabetesliverpancreasmulti-organ disease |
| spellingShingle | Moritz Liebmann Melissa Asuaje Pfeifer Katharina Grupe Stephan Scherneck Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model International Journal of Molecular Sciences estradiol prediabetes gestational diabetes liver pancreas multi-organ disease |
| title | Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model |
| title_full | Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model |
| title_fullStr | Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model |
| title_full_unstemmed | Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model |
| title_short | Estradiol (E2) Improves Glucose-Stimulated Insulin Secretion and Stabilizes GDM Progression in a Prediabetic Mouse Model |
| title_sort | estradiol e2 improves glucose stimulated insulin secretion and stabilizes gdm progression in a prediabetic mouse model |
| topic | estradiol prediabetes gestational diabetes liver pancreas multi-organ disease |
| url | https://www.mdpi.com/1422-0067/23/12/6693 |
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