Adaptive Changes in Glucose Homeostasis and Islet Function During Pregnancy: A Targeted Metabolomics Study in Mice
Notice bibliographique
Résumé
Objective: Pregnancy is a dynamic state involving multiple metabolic adaptions in various tissues including the endocrine pancreas. However, a detailed characterization of the maternal islet metabolome in relation to islet function and the ambient circulating metabolome during pregnancy has not been established. Methods: A timed-pregnancy mouse model was studied, and age-matched non-pregnant mice were used as controls. Targeted metabolomics was applied to fasting plasma and purified islets during each trimester of pregnancy. Glucose homeostasis and islet function was assessed. Bioinformatic analyses were performed to reveal the metabolic adaptive changes in plasma and islets, and to identify key metabolic pathways associated with pregnancy. Results: Fasting glucose and insulin were found to be significantly lower in pregnant mice compared to non-pregnant controls, throughout the gestational period. Additionally, pregnant mice had superior glucose excursions and greater insulin response to an oral glucose tolerance test. Interestingly, both alpha and beta cell proliferation were significantly enhanced in early to mid-pregnancy, leading to significantly increased islet size seen in mid to late gestation. When comparing the plasma metabolome of pregnant and non-pregnant mice, phospholipid and fatty acid metabolism pathways were found to be upregulated throughout pregnancy, whereas amino acid metabolism initially decreased in early through mid pregnancy, but then increased in late pregnancy. Conversely, in islets, amino acid metabolism was consistently enriched throughout pregnancy, with glycerophospholid and fatty acid metabolism was only upregulated in late pregnancy. Specific amino acids (glutamate, valine) and lipids (acyl-alkyl-PC, diacyl-PC, and sphingomyelin) were found to be significantly differentially expressed in islets of the pregnant mice compared to controls, which was possibly linked to enhanced insulin secretion and islet proliferation. Conclusion: Beta cell proliferation and function are elevated during pregnancy, and this is coupled to the enrichment of islet metabolites and metabolic pathways primarily associated with amino acid and glycerophospholipid metabolism. This study provides insight into metabolic adaptive changes in glucose homeostasis and islet function seen during pregnancy, which will provide a molecular rationale to further explore the regulation of maternal metabolism to avoid the onset of pregnancy disorders, including gestational diabetes.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».