The Role of Fatty Acid Signaling in Islet Beta-Cell Adaptation to Normal Pregnancy
| Autor: | Jee-Hye Kim, Viviane Delghingaro-Augusto, Jeng Yie Chan, D. Ross Laybutt, Joseph Proietto, Christopher J. Nolan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Blood Glucose
Glycerol insulin secretion Ppargc1a Endocrinology Diabetes and Metabolism Lipolysis fatty acid signaling Diseases of the endocrine glands. Clinical endocrinology Sprague-Dawley rat Endocrinology Pregnancy Insulin-Secreting Cells Animals hyperlipidemia Triglycerides Original Research Esterification Fatty Acids Glucose Tolerance Test RC648-665 Rats Liver fatty acid metabolism Female pancreatic islet beta-cell Oxidation-Reduction Glycogen Signal Transduction |
| Zdroj: | Frontiers in Endocrinology Frontiers in Endocrinology, Vol 12 (2022) |
| ISSN: | 1664-2392 |
| Popis: | BackgroundMaintenance of a normal fetal nutrient supply requires major adaptations in maternal metabolic physiology, including of the islet beta-cell. The role of lipid signaling processes in the mechanisms of islet beta-cell adaptation to pregnancy has been minimally investigated.ObjectiveTo determine the effects of pregnancy on islet fatty acid (FA) metabolic partitioning and FA augmentation of glucose-stimulated insulin secretion (GSIS).MethodsAge matched virgin, early pregnant (gestational day-11, G11) and late pregnant (G19) Sprague-Dawley rats were studied. Fasted and fed state biochemistry, oral glucose tolerance tests (OGTT), and fasted and post-OGTT liver glycogen, were determined to assess in vivo metabolic characteristics. In isolated islets, FA (BSA-bound palmitate 0.25 mmol/l) augmentation of GSIS, FA partitioning into esterification and oxidation processes using metabolic tracer techniques, lipolysis by glycerol release, triacylglycerols (TG) content, and the expression of key beta-cell genes were determined.ResultsPlasma glucose in pregnancy was lower, including during the OGTT (glucose area under the curve 0-120 min (AUC0-120); 655±24 versus 849±13 mmol.l-1.min; G19 vs virgin; P0-120; 97±7 versus 83±7 ng.ml-1.min; G19 vs virgin; not significant). Liver glycogen was depleted in fasted G19 rats with full recovery after oral glucose. Serum TG increased during pregnancy (4.4±0.4, 6.7±0.5; 17.1±1.5 mmol/l; virgin, G11, G19, PPPpargc1a, a key regulator of mitochondrial metabolism, was reduced by 51% in G11 and 64% in G19 pregnant rat islets compared to virgin rat islets (PConclusionA lowered set-point for islet and hepatic glucose homeostasis in the pregnant rat has been confirmed. Islet adaptation to pregnancy includes increased FA esterification, reduced FA oxidation, and enhanced FA augmentation of glucose-stimulated insulin secretion. |
| Databáze: | OpenAIRE |
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