941-P: Epiallopregnanolone Sulfate Is Reduced in Gestational Diabetes Mellitus and Induces Glucose-Stimulated Insulin Secretion
| Autor: | David R. McCance, Katharine F. Hunt, Franca Fraternali, David Andersson, James E. Bowe, Catherine Williamson, Mirko Giorgi, Stuart Bevan, Alice Mitchell, Hanns-Ulrich Marschall, Ivano Eberini, Hei Man Fan, Peter B. Jones |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
geography
medicine.medical_specialty Pregnancy geography.geographical_feature_category business.industry Endocrinology Diabetes and Metabolism medicine.disease Islet Calcium in biology Gestational diabetes chemistry.chemical_compound Endocrinology Isosakuranetin chemistry Internal medicine Internal Medicine medicine Gestation Glucose homeostasis Receptor business |
| Zdroj: | Diabetes. 70 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Introduction: Serum progesterone sulfate (P4S) concentrations increase in pregnancy and bind receptors that influence glucose homeostasis. We hypothesized that P4S modulate glucose homeostasis in pregnancy. Methods: Serum P4S were assayed using ultra-performance liquid chromatography- tandem mass spectrometry. Samples were studied in three separate patient groups: women with GDM (n=20) and matched healthy controls (n=38); participants (average 28 weeks’ gestation) from the upper (n=93) and lower (n=94) quartiles of fasting plasma glucose in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study; 11-13 week pregnant women with BMI≤25 or BMI≥35 who subsequently had uncomplicated pregnancies or developed GDM (n=50/group). Glucose-stimulated insulin secretion (GSIS) was quantified in isolated wild-type, Fxr-/- and Tgr5-/- mouse and human islets in the presence of P4S and TRPM3 inhibitor isosakuranetin (ISO). Intracellular calcium concentrations were measured after treatment with P4S in TRPM3 transfected HEK293. Computer modelling using Molecular Operating Environment generated 3D structures of TRPM3 and P4S binding. Results: Epiallopregnanolone sulfate (PM5S) concentrations were reduced in serum samples from the HAPO study participants with higher fasting plasma glucose (p Conclusion: PM5S increases GSIS and concentrations are reduced in the serum of women with GDM. The increased GSIS is mediated by TRPM3. Disclosure H. Fan: None. F. Fraternali: None. K. F. Hunt: None. J. Bowe: None. C. Williamson: Consultant; Self; GlaxoSmithKline plc., Mirum Pharmaceuticals. A. Mitchell: None. M. Giorgi: None. P. M. Jones: None. D. R. Mccance: None. D. A. Andersson: None. S. Bevan: None. H. Marschall: None. I. Eberini: None. Funding Tommy’s; Guy’s and St Thomas’ Biomedical Research Centre; National Health Service |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|