Lactation improves pancreatic β cell mass and function through serotonin production.

Abstract:

: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.

journal_name

Sci Transl Med

authors

Moon JH,Kim H,Kim H,Park J,Choi W,Choi W,Hong HJ,Ro HJ,Jun S,Choi SH,Banerjee RR,Shong M,Cho NH,Kim SK,German MS,Jang HC,Kim H

doi

10.1126/scitranslmed.aay0455

subject

Has Abstract

pub_date

2020-04-29 00:00:00

issue

541

eissn

1946-6234

issn

1946-6242

pii

12/541/eaay0455

journal_volume

12

pub_type

杂志文章
  • A molecular bandage for diseased muscle.

    abstract::MG53 promotes sarcolemmal repair in the mdx mouse model of Duchenne muscular dystrophy (Weisleder et al., this issue) and identifies a new protein therapeutic for muscle disease. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.3004082

    authors: Burkin DJ,Wuebbles RD

    更新日期:2012-06-20 00:00:00

  • Gastrointestinal synthetic epithelial linings.

    abstract::Epithelial tissues line the organs of the body, providing an initial protective barrier as well as a surface for nutrient and drug absorption. Here, we identified enzymatic components present in the gastrointestinal epithelium that can serve as selective means for tissue-directed polymerization. We focused on the smal...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.abc0441

    authors: Li J,Wang T,Kirtane AR,Shi Y,Jones A,Moussa Z,Lopes A,Collins J,Tamang SM,Hess K,Shakur R,Karandikar P,Lee JS,Huang HW,Hayward A,Traverso G

    更新日期:2020-08-26 00:00:00

  • Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

    abstract::Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision thro...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaa8791

    authors: Ashtari M,Zhang H,Cook PA,Cyckowski LL,Shindler KS,Marshall KA,Aravand P,Vossough A,Gee JC,Maguire AM,Baker CI,Bennett J

    更新日期:2015-07-15 00:00:00

  • Translational cancer research comes of age in Latin America.

    abstract::The U.S.-Latin America Cancer Research Network strives to expand translational research capabilities and forge new collaborations. ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aad5859

    authors: Investigators of the US–Latin America Cancer Research Network.

    更新日期:2015-12-23 00:00:00

  • Regulation of immune responses to protein therapeutics by transplacental induction of T cell tolerance.

    abstract::Central tolerance plays a key role in modulating immune responses to self and exogenous antigens. The absence of self-antigen expression, as in patients with genetic deficiencies, prevents the development of antigen-specific immune tolerance. Hence, a substantial number of patients develop neutralizing antibodies to t...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaa1957

    authors: Gupta N,Culina S,Meslier Y,Dimitrov J,Arnoult C,Delignat S,Gangadharan B,Lecerf M,Justesen S,Gouilleux-Gruart V,Salomon BL,Scott DW,Kaveri SV,Mallone R,Lacroix-Desmazes S

    更新日期:2015-02-18 00:00:00

  • An annexin A1-FPR1 interaction contributes to necroptosis of keratinocytes in severe cutaneous adverse drug reactions.

    abstract::Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, cutaneous adverse drug reactions that are accompanied by keratinocyte cell death. Dead keratinocytes from SJS/TEN lesions exhibited necrosis, by morphological criteria. Supernatant from peripheral blood mononuclear cells (PBMCs) ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3008227

    authors: Saito N,Qiao H,Yanagi T,Shinkuma S,Nishimura K,Suto A,Fujita Y,Suzuki S,Nomura T,Nakamura H,Nagao K,Obuse C,Shimizu H,Abe R

    更新日期:2014-07-16 00:00:00

  • Replacing and safeguarding pancreatic β cells for diabetes.

    abstract::Pluripotent stem cells are a scalable source of pancreatic cells for transplantation into patients with diabetes. Here, we describe how the field is gaining momentum toward a β cell replacement therapy. ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaa9359

    authors: Bruin JE,Rezania A,Kieffer TJ

    更新日期:2015-12-02 00:00:00

  • Age-related intimal stiffening enhances endothelial permeability and leukocyte transmigration.

    abstract::Age is the most significant risk factor for atherosclerosis; however, the link between age and atherosclerosis is poorly understood. During both aging and atherosclerosis progression, the blood vessel wall stiffens owing to alterations in the extracellular matrix. Using in vitro and ex vivo models of vessel wall stiff...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3002761

    authors: Huynh J,Nishimura N,Rana K,Peloquin JM,Califano JP,Montague CR,King MR,Schaffer CB,Reinhart-King CA

    更新日期:2011-12-07 00:00:00

  • Gga3 deletion and a GGA3 rare variant associated with late onset Alzheimer's disease trigger BACE1 accumulation in axonal swellings.

    abstract::Axonal dystrophy, indicative of perturbed axonal transport, occurs early during Alzheimer's disease (AD) pathogenesis. Little is known about the mechanisms underlying this initial sign of the pathology. This study proves that Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) loss of function, due to Gga3 g...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aba1871

    authors: Lomoio S,Willen R,Kim W,Ho KZ,Robinson EK,Prokopenko D,Kennedy ME,Tanzi RE,Tesco G

    更新日期:2020-11-18 00:00:00

  • Molecular profiling: moving away from tumor philately.

    abstract::Despite the remarkable enhancements in breast cancer classification and characterization, an exhaustive comprehension of the underlying carcinogenic processes and an accurate prediction of its clinical behavior are yet to be achieved. On the wave of recent scientific advances and clinical findings, new cutting-edge te...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3001329

    authors: Reis-Filho JS,Weigelt B,Fumagalli D,Sotiriou C

    更新日期:2010-09-01 00:00:00

  • Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions.

    abstract::The proinflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis and the course of inflammatory skin diseases, including psoriasis. Posttranscriptional activation of IL-1β is mediated by inflammasomes; however, the mechanisms triggering IL-1β processing remain unknown. Recently, cytosolic D...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3002001

    authors: Dombrowski Y,Peric M,Koglin S,Kammerbauer C,Göss C,Anz D,Simanski M,Gläser R,Harder J,Hornung V,Gallo RL,Ruzicka T,Besch R,Schauber J

    更新日期:2011-05-11 00:00:00

  • Brief suppression of Abcc8 prevents autodestruction of spinal cord after trauma.

    abstract::Spinal cord injury (SCI) is typically complicated by progressive hemorrhagic necrosis, an autodestructive process of secondary injury characterized by progressive enlargement of a hemorrhagic contusion during the first several hours after trauma. We assessed the role of Abcc8, which encodes sulfonylurea receptor 1 (SU...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000522

    authors: Simard JM,Woo SK,Norenberg MD,Tosun C,Chen Z,Ivanova S,Tsymbalyuk O,Bryan J,Landsman D,Gerzanich V

    更新日期:2010-04-21 00:00:00

  • Comment on "A small-molecule antivirulence agent for treating Clostridium difficile infection".

    abstract::New insights into the mechanism of action of ebselen, a small-molecule antivirulence agent that reduces disease pathology in a mouse model of Clostridium difficile infection, suggest a different molecular target may be responsible for its efficacy. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.aad8926

    authors: Beilhartz GL,Tam J,Zhang Z,Melnyk RA

    更新日期:2016-12-21 00:00:00

  • Assessing the safety of adjuvanted vaccines.

    abstract::Despite the very low risk-to-benefit ratio of vaccines, fear of negative side effects has discouraged many people from getting vaccinated, resulting in reemergence of previously controlled diseases such as measles, pertussis, and diphtheria. Part of this fear stems from the lack of public awareness of the many preclin...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.3002302

    authors: Ahmed SS,Plotkin SA,Black S,Coffman RL

    更新日期:2011-07-27 00:00:00

  • Tweaking the social network.

    abstract::Paving the way for clinical trials, a new study shows that a glutamate receptor antagonist reduces repetitive behavior and social deficits in a mouse model of autism spectrum disorder. ...

    journal_title:Science translational medicine

    pub_type: 评论,杂志文章

    doi:10.1126/scitranslmed.3004017

    authors: Gomez-Mancilla B

    更新日期:2012-04-25 00:00:00

  • Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration.

    abstract::Retinal prosthetic implants are the only approved treatment for retinitis pigmentosa, a disease of the eye that causes blindness through gradual degeneration of photoreceptors. An array of microelectrodes triggered by input from a camera stimulates surviving retinal neurons, with each electrode acting as a pixel. Unin...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aac4877

    authors: Weitz AC,Nanduri D,Behrend MR,Gonzalez-Calle A,Greenberg RJ,Humayun MS,Chow RH,Weiland JD

    更新日期:2015-12-16 00:00:00

  • Using health information technology to engage communities in health, education, and research.

    abstract::The August 2011 Clinical and Translational Science Awards conference "Using IT to Improve Community Health: How Health Care Reform Supports Innovation" convened four "Think Tank" sessions. Thirty individuals, representing various perspectives on community engagement, attended the "Health information technology (HIT) a...

    journal_title:Science translational medicine

    pub_type:

    doi:10.1126/scitranslmed.3003363

    authors: Marriott LK,Nelson DA,Allen S,Calhoun K,Eldredge CE,Kimminau KS,Lucero RJ,Pineda-Reyes F,Rumala BB,Varanasi AP,Wasser JS,Shannon J

    更新日期:2012-02-01 00:00:00

  • Aspirin and the risk of colorectal cancer in relation to the expression of 15-hydroxyprostaglandin dehydrogenase (HPGD).

    abstract::Aspirin use reduces the risk of colorectal neoplasia, at least in part, through inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase 2)-related pathways. Hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide) (15-PGDH, HPGD) is down-regulated in colorectal cancers and functions...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3008481

    authors: Fink SP,Yamauchi M,Nishihara R,Jung S,Kuchiba A,Wu K,Cho E,Giovannucci E,Fuchs CS,Ogino S,Markowitz SD,Chan AT

    更新日期:2014-04-23 00:00:00

  • IVIG-mediated protection against necrotizing pneumonia caused by MRSA.

    abstract::New therapeutic approaches are urgently needed to improve survival outcomes for patients with necrotizing pneumonia caused by Staphylococcus aureus One such approach is adjunctive treatment with intravenous immunoglobulin (IVIG), but clinical practice guidelines offer conflicting recommendations. In a preclinical rabb...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aag1153

    authors: Diep BA,Le VT,Badiou C,Le HN,Pinheiro MG,Duong AH,Wang X,Dip EC,Aguiar-Alves F,Basuino L,Marbach H,Mai TT,Sarda MN,Kajikawa O,Matute-Bello G,Tkaczyk C,Rasigade JP,Sellman BR,Chambers HF,Lina G

    更新日期:2016-09-21 00:00:00

  • Amphiphysin 2 modulation rescues myotubular myopathy and prevents focal adhesion defects in mice.

    abstract::Centronuclear myopathies (CNMs) are severe diseases characterized by muscle weakness and myofiber atrophy. Currently, there are no approved treatments for these disorders. Mutations in the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for X-linked CNM (XLCNM), also called myotubular myopathy, wher...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aav1866

    authors: Lionello VM,Nicot AS,Sartori M,Kretz C,Kessler P,Buono S,Djerroud S,Messaddeq N,Koebel P,Prokic I,Hérault Y,Romero NB,Laporte J,Cowling BS

    更新日期:2019-03-20 00:00:00

  • Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer.

    abstract::Epidermal growth factor receptor (EGFR) gene mutations (G719X, exon 19 deletions/insertions, L858R, and L861Q) predict favorable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). However, EGFR exon 20 insertion mutations (~10% of all EGFR mutations) are generally assoc...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3007205

    authors: Yasuda H,Park E,Yun CH,Sng NJ,Lucena-Araujo AR,Yeo WL,Huberman MS,Cohen DW,Nakayama S,Ishioka K,Yamaguchi N,Hanna M,Oxnard GR,Lathan CS,Moran T,Sequist LV,Chaft JE,Riely GJ,Arcila ME,Soo RA,Meyerson M,Eck MJ,K

    更新日期:2013-12-18 00:00:00

  • Atherosclerosis drug development in jeopardy: the need for predictive biomarkers of treatment response.

    abstract::The limited predictability of phase II biomarkers for atherosclerosis outcomes in phase III studies stands in contrast to the number and varied types of biomarkers--soluble, imaging, and functional--that have been used in a diverse array of trials. Although collectively abundant, these biomarker data exist in a fragme...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3002029

    authors: Fryburg DA,Vassileva MT

    更新日期:2011-03-02 00:00:00

  • Off-target lapatinib activity sensitizes colon cancer cells through TRAIL death receptor up-regulation.

    abstract::Lapatinib, a dual HER2/EGFR (human epidermal growth factor receptor 2/epidermal growth factor receptor) inhibitor, is a recently approved targeted therapy for metastatic breast cancer. Because lapatinib enhances the efficacy of the chemotherapeutic agent capecitabine in breast cancer patients, we tested whether lapati...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3001384

    authors: Dolloff NG,Mayes PA,Hart LS,Dicker DT,Humphreys R,El-Deiry WS

    更新日期:2011-06-08 00:00:00

  • Epidermal electronics for noninvasive, wireless, quantitative assessment of ventricular shunt function in patients with hydrocephalus.

    abstract::Hydrocephalus is a common and costly neurological condition caused by the overproduction and/or impaired resorption of cerebrospinal fluid (CSF). The current standard of care, ventricular catheters (shunts), is prone to failure, which can result in nonspecific symptoms such as headaches, dizziness, and nausea. Current...

    journal_title:Science translational medicine

    pub_type: 临床试验,杂志文章

    doi:10.1126/scitranslmed.aat8437

    authors: Krishnan SR,Ray TR,Ayer AB,Ma Y,Gutruf P,Lee K,Lee JY,Wei C,Feng X,Ng B,Abecassis ZA,Murthy N,Stankiewicz I,Freudman J,Stillman J,Kim N,Young G,Goudeseune C,Ciraldo J,Tate M,Huang Y,Potts M,Rogers JA

    更新日期:2018-10-31 00:00:00

  • The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy.

    abstract::Patients undergoing surgical resection of primary breast tumors confront a risk for metastatic recurrence that peaks sharply 12 to 18 months after surgery. The cause of early metastatic relapse in breast cancer has long been debated, with many ascribing these relapses to the natural progression of the disease. Others ...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aan3464

    authors: Krall JA,Reinhardt F,Mercury OA,Pattabiraman DR,Brooks MW,Dougan M,Lambert AW,Bierie B,Ploegh HL,Dougan SK,Weinberg RA

    更新日期:2018-04-11 00:00:00

  • Estimation of polio infection prevalence from environmental surveillance data.

    abstract::A major obstacle to eradicating polio is that poliovirus from endemic countries can be reintroduced to polio-free countries. Environmental surveillance (ES) can detect poliovirus from sewage or wastewaters samples, even in the absence of patients with paralysis. ES is underused, in part because its sensitivity is unkn...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aaf6786

    authors: Berchenko Y,Manor Y,Freedman LS,Kaliner E,Grotto I,Mendelson E,Huppert A

    更新日期:2017-03-29 00:00:00

  • Production and transplantation of bioengineered lung into a large-animal model.

    abstract::The inability to produce perfusable microvasculature networks capable of supporting tissue survival and of withstanding physiological pressures without leakage is a fundamental problem facing the field of tissue engineering. Microvasculature is critically important for production of bioengineered lung (BEL), which req...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aao3926

    authors: Nichols JE,La Francesca S,Niles JA,Vega SP,Argueta LB,Frank L,Christiani DC,Pyles RB,Himes BE,Zhang R,Li S,Sakamoto J,Rhudy J,Hendricks G,Begarani F,Liu X,Patrikeev I,Pal R,Usheva E,Vargas G,Miller A,Woodson L,

    更新日期:2018-08-01 00:00:00

  • Immune-mediated pathology in Duchenne muscular dystrophy.

    abstract::Immunological and inflammatory processes downstream of dystrophin deficiency as well as metabolic abnormalities, defective autophagy, and loss of regenerative capacity all contribute to muscle pathology in Duchenne muscular dystrophy (DMD). These downstream cascades offer potential avenues for pharmacological interven...

    journal_title:Science translational medicine

    pub_type: 杂志文章,评审

    doi:10.1126/scitranslmed.aaa7322

    authors: Rosenberg AS,Puig M,Nagaraju K,Hoffman EP,Villalta SA,Rao VA,Wakefield LM,Woodcock J

    更新日期:2015-08-05 00:00:00

  • Oxytocin antagonism prevents pregnancy-associated aortic dissection in a mouse model of Marfan syndrome.

    abstract::Women with Marfan syndrome (MFS) are at high risk for pregnancy-associated aortic dissection. Pathogenic models that singularly invoke hemodynamic stress are difficult to reconcile with predominant postnatal occurrence of aortic tear, often occurring weeks to months after delivery. In consideration of events that peak...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.aat4822

    authors: Habashi JP,MacFarlane EG,Bagirzadeh R,Bowen C,Huso N,Chen Y,Bedja D,Creamer TJ,Rykiel G,Manning M,Huso D,Dietz HC

    更新日期:2019-05-01 00:00:00

  • Liberating health data for clinical research applications.

    abstract::Global investments in health information technology (HIT) in the form of electronic health record systems represent important new strategies to improve the quality and efficiency of health care. These potential benefits of HIT will not be achieved without direct attention to the use of health care information for clin...

    journal_title:Science translational medicine

    pub_type: 杂志文章

    doi:10.1126/scitranslmed.3000764

    authors: Nadler JJ,Downing GJ

    更新日期:2010-02-10 00:00:00