Abstract:
:Diabetes, a disease in which the body does not produce or use insulin properly, is a serious global health problem. Gut polypeptides secreted in response to food intake, such as glucagon-like peptide-1 (GLP-1), are potent incretin hormones that enhance the glucose-dependent secretion of insulin from pancreatic beta cells. Free fatty acids (FFAs) provide an important energy source and also act as signaling molecules in various cellular processes, including the secretion of gut incretin peptides. Here we show that a G-protein-coupled receptor, GPR120, which is abundantly expressed in intestine, functions as a receptor for unsaturated long-chain FFAs. Furthermore, we show that the stimulation of GPR120 by FFAs promotes the secretion of GLP-1 in vitro and in vivo, and increases circulating insulin. Because GLP-1 is the most potent insulinotropic incretin, our results indicate that GPR120-mediated GLP-1 secretion induced by dietary FFAs is important in the treatment of diabetes.
journal_name
Nat Medjournal_title
Nature medicineauthors
Hirasawa A,Tsumaya K,Awaji T,Katsuma S,Adachi T,Yamada M,Sugimoto Y,Miyazaki S,Tsujimoto Gdoi
10.1038/nm1168keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
90-4issue
1eissn
1078-8956issn
1546-170Xpii
nm1168journal_volume
11pub_type
杂志文章相关文献
NATURE MEDICINE文献大全abstract::Some individuals remain uninfected with human immunodeficiency virus type-1 (HIV-1) despite multiple high-risk sexual exposures. We studied a cohort of 25 subjects with histories of multiple high-risk sexual exposures to HIV-1 and found that their CD8+ lymphocytes had greater anti-HIV-1 activity than did CD8+ lymphocy...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0496-412
更新日期:1996-04-01 00:00:00
abstract::Hematopoietic stem and progenitor cells (HSPC) are endowed with the role of generating and maintaining lifelong the extremely diverse pool of blood cells1. Clinically, transplantation of human HSPC from an allogeneic healthy donor or infusion of autologous gene-corrected HSPC can effectively replenish defective blood ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-018-0195-3
更新日期:2018-11-01 00:00:00
abstract::Immune evasion is an emerging hallmark of cancer progression. However, functional studies to understand the role of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment are limited by the lack of available specific cell surface markers. We adapted a competitive peptide phage display platform to ident...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3560
更新日期:2014-06-01 00:00:00
abstract::The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing o...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-018-0323-0
更新日期:2019-03-01 00:00:00
abstract::Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival1,2. Here, to explore the feasibility, safety and immunobiological effects of PD-1 ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-018-0339-5
更新日期:2019-03-01 00:00:00
abstract::Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for the condition because of limited understanding of its pathogenesis. We show that transforming growth factor β1 (TGF-β1) is activated in subchondral bone in response to altered mechanical loading in an anteri...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3143
更新日期:2013-06-01 00:00:00
abstract::The human CD4 molecule (hCD4) is expressed on T lymphocytes and macrophages and acts as a key component of the cellular receptor for HIV. At baseline, hCD4 transgenic mice expressed hCD4 on microglia, the resident mononuclear phagocytes of the brain, and showed no neuronal damage. Activation of brain microglia by peri...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0498-441
更新日期:1998-04-01 00:00:00
abstract::HIV-specific mucosal and cellular immunity was analyzed in heterosexual couples discordant for HIV status in serum and in HIV-unexposed controls. HIV-specific IgA but not IgG was present in urine and vaginal wash samples from HIV-exposed seronegative individuals (ESN), whereas both IgA and IgG were observed in their H...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1197-1250
更新日期:1997-11-01 00:00:00
abstract::Transcription factor FoxO1 promotes hepatic glucose production. Genetic inhibition of FoxO1 function prevents diabetes in experimental animal models, providing impetus to identify pharmacological approaches to modulate this function. Altered Notch signaling is evident in tumorigenesis, and Notch antagonists are in cli...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2378
更新日期:2011-07-31 00:00:00
abstract::We evaluated the ability of neonatal porcine islets to engraft and restore glucose control in pancreatectomized rhesus macaques. Although porcine islets transplanted into nonimmunosuppressed macaques were rapidly rejected by a process consistent with cellular rejection, recipients treated with a CD28-CD154 costimulati...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1375
更新日期:2006-03-01 00:00:00
abstract::In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibit...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3822
更新日期:2015-04-01 00:00:00
abstract::The search for immunosuppressant drugs to increase the success of organ transplantation led to the discovery of the immunophilins, proteins that interface with a range of signal transduction systems inside cells, especially in the nervous and immune systems. Here we review how these interesting molecules work and cons...
journal_title:Nature medicine
pub_type: 杂志文章,评审
doi:10.1038/nm0195-32
更新日期:1995-01-01 00:00:00
abstract::Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to a...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-018-0052-4
更新日期:2018-07-01 00:00:00
abstract::The inwardly rectifying K(+) channel Kir6.1 forms K(+) channels by coupling with a sulfonylurea receptor in reconstituted systems, but the physiological roles of Kir6.1-containing K(+) channels have not been determined. We report here that mice lacking the gene encoding Kir6.1 (known as Kcnj8) have a high rate of sudd...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0502-466
更新日期:2002-05-01 00:00:00
abstract::Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that is initiated when self-reactive T cells enter the brain and become locally activated after encountering their specific nervous antigens. When and where the disease-relevant antigen encounters occur is unclear. Here we combined fluores...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3182
更新日期:2013-06-01 00:00:00
abstract::Overexpression of the normally imprinted fetal insulin-like growth factor II (IGF2) has been implicated in the pathogenesis of the cancer-predisposing Beckwith-Wiedemann syndrome (BWS). We have detected constitutional relaxation of imprinting of IGF2 in four children with somatic overgrowth who do not show diagnostic ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0396-311
更新日期:1996-03-01 00:00:00
abstract::Movement towards or away from a given stimulus guides the directional migration of prokaryotes, simple eukaryotes and neurons. As bi-directional cues may influence entry and exit of immune effector cells from tissue sites, we evaluated the migratory responses of T-cell subsets to varying concentrations of the chemokin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/75022
更新日期:2000-05-01 00:00:00
abstract::With an ever increasing number of people taking numerous medications, the need to safely administer drugs and limit unintended side effects has never been greater. Antidote control remains the most direct means to counteract acute side effects of drugs, but, unfortunately, it has been challenging and cost prohibitive ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.1990
更新日期:2009-10-01 00:00:00
abstract::Hutchinson-Gilford progeria syndrome (HGPS) is a rare lethal genetic disorder characterized by symptoms reminiscent of accelerated aging. The major underlying genetic cause is a substitution mutation in the gene coding for lamin A, causing the production of a toxic isoform called progerin. Here we show that reduction ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-019-0343-4
更新日期:2019-03-01 00:00:00
abstract::Regulatory T cells (T(reg) cells) suppress autoreactive immune responses and limit the efficacy of tumor vaccines; however, it remains a challenge to selectively eliminate or inhibit T(reg) cells. In this study, the zinc-finger A20, a negative regulator of the Toll-like receptor and tumor necrosis factor receptor sign...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1721
更新日期:2008-03-01 00:00:00
abstract::Synovial tissue affected by rheumatoid arthritis is characterized by proliferation, which leads to irreversible cartilage and bone destruction. Current and experimental treatments have been aimed mainly at correcting the underlying immune abnormalities, but these treatments often prove ineffective in preventing the in...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/10480
更新日期:1999-07-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature medicine
pub_type: 已发布勘误
doi:10.1038/s41591-020-0924-2
更新日期:2020-07-01 00:00:00
abstract::Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthes...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1204
更新日期:2005-04-01 00:00:00
abstract::Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain el...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2124
更新日期:2010-04-01 00:00:00
abstract::Single-cell genomics is essential to chart tumor ecosystems. Although single-cell RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated from fresh tumors, single-nucleus RNA-Seq (snRNA-Seq) is needed to profile frozen or hard-to-dissociate tumors. Each requires customization to different tissue and tumor types, posi...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-020-0844-1
更新日期:2020-05-01 00:00:00
abstract::Natalizumab (NZM), a humanized monoclonal IgG4 antibody to α4 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS)1,2, but in about 6% of the cases persistent neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation3,4. To understand the basis of the ADA ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-019-0568-2
更新日期:2019-09-01 00:00:00
abstract::Together with recent advances in the processing and culture of human tissue, bioengineering, xenotransplantation and genome editing, Induced pluripotent stem cells (iPSCs) present a range of new opportunities for the study of human cancer. Here we discuss the main advantages and limitations of iPSC modeling, and how t...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4238
更新日期:2016-12-06 00:00:00
abstract::Autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, serves as a cell survival mechanism in starving cells. Although altered autophagy has been observed in various heart diseases, including cardiac hypertrophy and heart failure, it remains unclear whether autophagy plays a...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1574
更新日期:2007-05-01 00:00:00
abstract::The acceleration of atherosclerosis by polygenic (essential) hypertension is well-characterized in humans; however, the lack of an animal model that simulates human disease hinders the elucidation of pathogenic mechanisms. We report here a transgenic atherosclerosis-polygenic hypertension model in Dahl salt-sensitive ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/70956
更新日期:1999-12-01 00:00:00
abstract::Use of wearable devices that monitor physical activity is projected to increase more than fivefold per half-decade1. We investigated how device-based physical activity energy expenditure (PAEE) and different intensity profiles were associated with all-cause mortality. We used a network harmonization approach to map do...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-020-1012-3
更新日期:2020-09-01 00:00:00