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Breastfeeding Helps Prevent Mothers from Developing Diabetes after Childbirth
A team of South Korean researchers found that lactation can lower the incidence and reduce the risk of maternal postpartum diabetes. The researchers identified that lactation increases the mass and function of pancreatic beta cells through serotonin production. The team suggested that sustained improvements in pancreatic beta cells, which can last for years even after the cessation of lactation, improve mothers’ metabolic health in addition to providing health benefits for infants. Pregnancy imposes a substantial metabolic burden on women through weight gain and increased insulin resistance. Various other factors, including a history of gestational diabetes, maternal age, and obesity, further affect women’s risk of progressing to diabetes after delivery, and the risk of postpartum diabetes increases more in women who have had gestational diabetes and/or repeated deliveries. Diabetes-related complications include damage to blood vessels, which can lead to cardiovascular and cerebrovascular diseases such as heart attack and stroke, and problems with the nerves, eyes, kidneys, and many more. Since diabetes can pose a serious threat to mothers’ metabolic health, the management of maternal metabolic risk factors is important, especially in the peripartum period. Previous epidemiological studies have reported that lactation reduces the risk of postpartum diabetes, but the mechanisms underlying this benefit have remained elusive. The study, published in Science Translational Medicine on April 29, explains the biology underpinning this observation on the beneficial effects of lactation. Professor Hail Kim from the Graduate School of Medical Science and Engineering at KAIST led and jointly conducted the study in conjunction with researchers from the Seoul National University Bundang Hospital (SNUBH) and Chungnam National University (CNU) in Korea, and the University of California, San Francisco (UCSF) in the US. In their study, the team observed that the milk-secreting hormone ‘prolactin’ in lactating mothers not only promotes milk production, but also plays a major role in stimulating insulin-secreting pancreatic beta cells that regulate blood glucose in the body. The researchers also found that ‘serotonin’, known as a chemical that contributes to wellbeing and happiness, is produced in pancreatic beta cells during lactation. Serotonin in pancreatic beta cells act as an antioxidant and reduce oxidative stress, making mothers’ beta cells healthier. Serotonin also induces the proliferation of beta cells, thereby increasing the beta cell mass and helping maintain proper glucose levels. The research team conducted follow-up examinations on a total of 174 postpartum women, 85 lactated and 99 non-lactated, at two months postpartum and annually thereafter for at least three years. The results demonstrated that mothers who had undergone lactation improved pancreatic beta cell mass and function, and showed improved glucose homeostasis with approximately 20mg/dL lower glucose levels, thereby reducing the risk of postpartum diabetes in women. Surprisingly, this beneficial effect was maintained after the cessation of lactation, for more than three years after delivery. Professor Kim said, “We are happy to prove that lactation benefits female metabolic health by improving beta cell mass and function as well as glycemic control.” “Our future studies on the modulation of the molecular serotonergic pathway in accordance with the management of maternal metabolic risk factors may lead to new therapeutics to help prevent mothers from developing metabolic disorders,” he added. This work was supported by grants from the National Research Foundation (NRF) and the National Research Council of Science and Technology (NST) of Korea, the National Institutes of Health (NIH), the Larry L. Hillblom Foundation, and the Health Fellowship Foundation. Image credit: Professor Hail Kim, KAIST Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only. Publication: Moon, J. H et al. (2020) ‘Lactation improves pancreatic β cell mass and function through serotonin production.’ Science Translational Medicine, 12, eaay0455. Available online at https://doi.org/10.1126/scitranslmed.aay0455 Profile: Hail Kim, MD, PhD email@example.com Associate Professor Graduate School of Medical Science and Engineering (GSMSE) Korea Advanced Institute of Science and Technology (KAIST) Profile: Hak Chul Jang, MD, PhD firstname.lastname@example.org Professor Division of Endocrinology and Metabolism Seoul National University Bundang Hospital (SNUBH) President Korean Diabetes Association Profile: Joon Ho Moon, MD, PhD email@example.com Clinical Fellow Division of Endocrinology and Metabolism SNUBH Profile: Hyeongseok Kim, MD, PhD firstname.lastname@example.org Assistant Professor Chungnam National University (CNU) Profile: Professor Michael S. German, MD Michael.German@ucsf.edu Professor Diabetes Center University of California, San Francisco (UCSF) (END)
Newly Identified Meningeal Lymphatic Vessels Answers the Key Questions on Brain Clearance
(Figure: Schematic images of location and features of meningeal lymphatic vessels and their changes associated with ageing.) Just see what happens when your neighborhood’s waste disposal system is out of service. Not only do the piles of trash stink but they can indeed hinder the area’s normal functioning. That is also the case when the brain’s waste management is on the blink. The buildup of toxic proteins in the brain causes a massive damage to the nerves, leading to cognitive dysfunction and increased probability of developing neurodegenerative disorders such as Alzheimer's disease. Though the brain drains its waste via the cerebrospinal fluid (CSF), little has been understood about an accurate route for the brain’s cleansing mechanism. Medical scientists led by Professor Gou Young Koh at the Graduate School of Medical Science and Engineering have reported the basal side of the skull as the major route, so called “hotspot” for CSF drainage. They found that basal meningeal lymphatic vessels (mLVs) function as the main plumbing pipes for CSF. They confirmed macromolecules in the CSF mainly runs through the basal mLVs. Notably, the team also revealed that the brain’s major drainage system, specifically basal mLVs are impaired with aging. Their findings have been reported in the journal Nature on July 24. Throughout our body, excess fluids and waste products are removed from tissues via lymphatic vessels. It was only recently discovered that the brain also has a lymphatic drainage system. mLVs are supposed to carry waste from the brain tissue fluid and the CSF down the deep cervical lymph nodes for disposal. Still scientist are left with one perplexing question — where is the main exit for the CSF? Though mLVs in the upper part of the skull (dorsal meningeal lymphatic vessels) were reported as the brain’s clearance pathways in 2014, no substantial drainage mechanism was observed in that section. “As a hidden exit for CSF, we looked into the mLVs trapped within complex structures at the base of the skull,” says Dr. Ji Hoon Ahn, the first author of this study. The researchers used several techniques to characterize the basal mLVs in detail. They used a genetically engineered lymphatic-reporter mouse model to visualize mLVs under a fluorescence microscope. By performing a careful examination of the mice skull, they found distinctive features of basal mLVs that make them suitable for CSF uptake and drainage. Just like typical functional lymphatic vessels, basal mLVs are found to have abundant lymphatic vessel branches with finger-like protrusions. Additionally, valves inside the basal mLVs allow the flow to go in one direction. In particular, they found that the basal mLVs are closely located to the CSF. Dr. Hyunsoo Cho, the first author of this study explains, “All up, it seemed a solid case that basal mLVs are the brain’s main clearance pathways. The researchers verified such specialized morphologic characteristics of basal mLVs indeed facilitate the CSF uptake and drainage. Using CSF contrast-enhanced magnetic resonance imaging in a rat model, they found that CSF is drained preferentially through the basal mLVs. They also utilized a lymphatic-reporter mouse model and discovered that fluorescence-tagged tracer injected into the brain itself or the CSF is cleared mainly through the basal mLVs. Jun-Hee Kim, the first author of this study notes, “We literally saw that the brain clearance mechanism utilizing basal outflow route to exit the skull. It has long been suggested that CSF turnover and drainage declines with ageing. However, alteration of mLVs associated with ageing is poorly understood. In this study, the researchers observed changes of mLVs in young (3-month-old) and aged (24~27-months-old) mice. They found that the structure of the basal mLVs and their lymphatic valves in aged mice become severely flawed, thus hampering CSF clearance. The corresponding author of this study, Dr. Koh says, “By characterizing the precise route for fluids leaving the brain, this study improves our understanding on how waste is cleared from the brain. Our findings also provide further insights into the role of impaired CSF clearance in the development of age-related neurodegenerative diseases.” Many current therapies for Alzheimer’s disease target abnormally accumulated proteins, such as beta-amyloid. By mapping out a precise route for the brain’s waste clearance system, this study may be able to help find ways to improve the brain’s cleansing function. Such breakthrough might become quite a sensational strategy for eliminating the buildup of aging-related toxic proteins. “It definitely warrants more extensive investigation of mLVs in patients with age-related neurodegenerative disease such as Alzheimer’s disease prior to clinical investigation,” adds Professor Koh.
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