Moon Joon Ho, Kim Hyeongseok, Kim Hyunki, Park Jungsun, Choi Wonsuk, Choi Wongun, Hong Hyun Jung, Ro Hyun-Joo, Jun Sangmi, Choi Sung Hee, Banerjee Ronadip R, Shong Minho, Cho Nam Han, Kim Seung K, German Michael S, Jang Hak Chul, Kim Hail
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.
Sci Transl Med. 2020 Apr 29;12(541). doi: 10.1126/scitranslmed.aay0455.
Pregnancy imposes a substantial metabolic burden on women through weight gain and insulin resistance. Lactation reduces the risk of maternal postpartum diabetes, but the mechanisms underlying this benefit are unknown. Here, we identified long-term beneficial effects of lactation on β cell function, which last for years after the cessation of lactation. We analyzed metabolic phenotypes including β cell characteristics in lactating and non-lactating humans and mice. Lactating and non-lactating women showed comparable glucose tolerance at 2 months after delivery, but after a mean of 3.6 years, glucose tolerance in lactated women had improved compared to non-lactated women. In humans, the disposition index, a measure of insulin secretory function of β cells considering the degree of insulin sensitivity, was higher in lactated women at 3.6 years after delivery. In mice, lactation improved glucose tolerance and increased β cell mass at 3 weeks after delivery. Amelioration of glucose tolerance and insulin secretion were maintained up to 4 months after delivery in lactated mice. During lactation, prolactin induced serotonin production in β cells. Secreted serotonin stimulated β cell proliferation through serotonin receptor 2B in an autocrine and paracrine manner. In addition, intracellular serotonin acted as an antioxidant to mitigate oxidative stress and improved β cell survival. Together, our results suggest that serotonin mediates the long-term beneficial effects of lactation on female metabolic health by increasing β cell proliferation and reducing oxidative stress in β cells.
怀孕通过体重增加和胰岛素抵抗给女性带来巨大的代谢负担。哺乳可降低母亲产后患糖尿病的风险，但其潜在机制尚不清楚。在此，我们确定了哺乳对β细胞功能的长期有益影响，这种影响在停止哺乳后可持续数年。我们分析了哺乳期和非哺乳期人类及小鼠的代谢表型，包括β细胞特征。哺乳期和非哺乳期女性在分娩后2个月时的糖耐量相当，但平均3.6年后，哺乳女性的糖耐量相比未哺乳女性有所改善。在人类中，分娩后3.6年时，考虑到胰岛素敏感性程度的β细胞胰岛素分泌功能指标——处置指数，在哺乳女性中更高。在小鼠中，哺乳在分娩后3周时改善了糖耐量并增加了β细胞质量。在哺乳小鼠中，糖耐量和胰岛素分泌的改善在分娩后长达4个月时得以维持。在哺乳期间，催乳素诱导β细胞产生血清素。分泌的血清素通过血清素受体2B以自分泌和旁分泌方式刺激β细胞增殖。此外，细胞内血清素作为一种抗氧化剂减轻氧化应激并改善β细胞存活。总之，我们的结果表明，血清素通过增加β细胞增殖和减少β细胞氧化应激来介导哺乳对女性代谢健康的长期有益影响。
