Department of Pharmacology & Therapeutics, University of Manitoba.
Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme of the Children's Hospital Research Institute of Manitoba, University of Manitoba.
J Physiol. 2019 Aug;597(16):4175-4192. doi: 10.1113/JP278082. Epub 2019 Jul 21.
Maternal resveratrol (RESV) administration in gestational diabetes (GDM) restored normoglycaemia and insulin secretion. GDM-induced obesity was prevented in male GDM+RESV offspring but not in females. GDM+RESV offspring exhibited improved glucose tolerance and insulin sensitivity. GDM+RESV restored hepatic glucose homeostasis in offspring. Glucose-stimulated insulin secretion was enhanced in GDM+RESV offspring.
Gestational diabetes (GDM), the most common complication of pregnancy, is associated with adverse metabolic health outcomes in offspring. Using a rat model of diet-induced GDM, we investigated whether maternal resveratrol (RESV) supplementation (147 mg kg day ) in the third week of pregnancy could improve maternal glycaemia and protect the offspring from developing metabolic dysfunction. Female Sprague-Dawley rats consumed a high-fat and sucrose (HFS) diet to induce GDM. Lean controls consumed a low-fat (LF) diet. In the third trimester, when maternal hyperglycaemia was observed, the HFS diet was supplemented with RESV. At weaning, offspring were randomly assigned a LF or HFS diet until 15 weeks of age. In pregnant dams, RESV restored glucose tolerance, normoglycaemia and improved insulin secretion. At 15 weeks of age, GDM+RESV-HFS male offspring were less obese than the GDM-HFS offspring. By contrast, the female GDM+RESV-HFS offspring were similarly as obese as the GDM-HFS group. Hepatic steatosis, insulin resistance, glucose intolerance and dysregulated gluconeogenesis were observed in the male GDM offspring and were attenuated in the offspring of GDM+RESV dams. The dysregulation of several metabolic genes (e.g. ppara, lpl, pepck and g6p) in the livers of GDM offspring was attenuated in the GDM+RESV offspring group. Glucose stimulated insulin secretion was also improved in the islets from offspring of GDM+RESV dams. Thus, maternal RESV supplementation during the third trimester of pregnancy and lactation induced several beneficial metabolic health outcomes for both mothers and offspring. Therefore, RESV could be an alternative to current GDM treatments.
母体白藜芦醇（RESV）在妊娠期糖尿病（GDM）中的给药恢复了正常血糖和胰岛素分泌。雄性 GDM+RESV 后代的 GDM 诱导性肥胖得到预防，但雌性后代则不然。GDM+RESV 后代表现出改善的葡萄糖耐量和胰岛素敏感性。GDM+RESV 恢复了后代的肝葡萄糖稳态。葡萄糖刺激的胰岛素分泌在 GDM+RESV 后代中增强。
妊娠糖尿病（GDM）是最常见的妊娠并发症，与后代代谢健康不良结局相关。使用饮食诱导的 GDM 大鼠模型，我们研究了母体白藜芦醇（RESV）补充（妊娠第 3 周 147mgkg -1 day -1 ）是否可以改善母体血糖并防止后代发生代谢功能障碍。雌性 Sprague-Dawley 大鼠摄入高脂肪和蔗糖（HFS）饮食以诱导 GDM。瘦对照组摄入低脂（LF）饮食。在第三个三个月，当观察到母体高血糖时，HFS 饮食中补充 RESV。在断奶时，将后代随机分配到 LF 或 HFS 饮食中，直到 15 周龄。在妊娠母鼠中，RESV 恢复了葡萄糖耐量、正常血糖和改善的胰岛素分泌。在 15 周龄时，GDM+RESV-HFS 雄性后代比 GDM-HFS 后代肥胖程度低。相比之下，GDM+RESV-HFS 雌性后代与 GDM-HFS 组肥胖程度相似。雄性 GDM 后代的肝脂肪变性、胰岛素抵抗、葡萄糖不耐受和糖异生失调，以及 GDM+RESV 母鼠后代的代谢基因（例如 ppara、lpl、pepck 和 g6p）的失调在 GDM+RESV 后代组中减弱。葡萄糖刺激的胰岛素分泌也在 GDM+RESV 母鼠后代的胰岛中得到改善。因此，妊娠第三个三个月和哺乳期母体 RESV 补充对母亲和后代都产生了多种有益的代谢健康结果。因此，RESV 可能是目前 GDM 治疗的替代方法。
