Lactation improves pancreatic β cell mass and function through serotonin production.
Joon Ho MoonHyeongseok KimHyunki KimJungsun ParkWonsuk ChoiWongun ChoiHyun Jung HongHyun-Joo RoSangmi JunSung Hee ChoiRonadip R BanerjeeMinho ShongNam Han ChoSeung K KimMichael S GermanHak Chul JangHail KimPublished in: Science translational medicine (2021)
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.
Keyphrases
- dairy cows
- polycystic ovary syndrome
- induced apoptosis
- oxidative stress
- pregnancy outcomes
- human milk
- cell proliferation
- insulin resistance
- weight gain
- cell cycle arrest
- type diabetes
- high fat diet induced
- single cell
- body mass index
- cell therapy
- healthcare
- diabetic rats
- public health
- dna damage
- breast cancer risk
- birth weight
- signaling pathway
- heat stress
- cervical cancer screening
- pregnant women
- cardiovascular disease
- low birth weight
- cell death
- adipose tissue
- pi k akt
- ischemia reperfusion injury
- social media
- preterm infants
- preterm birth
- gestational age
- cell cycle
- health promotion
- high glucose