دورية أكاديمية
أعرض في EDS

Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival.

التفاصيل البيبلوغرافية
العنوان: Loss of Free Fatty Acid Receptor 2 leads to impaired islet mass and beta cell survival.
المؤلفون: Villa SR; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Priyadarshini M; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Fuller MH; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Bhardwaj T; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Brodsky MR; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Angueira AR; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Mosser RE; Vanderbilt University, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Nashville, TN, USA., Carboneau BA; Vanderbilt University, Department of Molecular Physiology and Biophysics, Nashville, TN, USA., Tersey SA; Department of Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA., Mancebo H; Multispan Inc., Hayward, CA, USA., Gilchrist A; Midwestern University Department of Pharmaceutical Sciences, Downers Grove, IL, USA., Mirmira RG; Department of Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Medicine, Indiana University School of Medicine, Indiana University, Indianapolis, IN, USA., Gannon M; Vanderbilt University, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Nashville, TN, USA.; Vanderbilt University, Department of Molecular Physiology and Biophysics, Nashville, TN, USA.; Tennessee Valley Health Authority, Department of Veterans Affairs, Nashville, TN, USA., Layden BT; Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.
المصدر: Scientific reports [Sci Rep] 2016 Jun 21; Vol. 6, pp. 28159. Date of Electronic Publication: 2016 Jun 21.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Diabetes Mellitus, Type 2/*metabolism , Insulin-Secreting Cells/*metabolism , Pancreas/*pathology , Receptors, Cell Surface/*metabolism, Animals ; Cell Survival ; Cells, Cultured ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/pathology ; Fatty Acids, Nonesterified/metabolism ; Fatty Acids, Volatile/metabolism ; Humans ; Insulin Resistance ; Insulin-Secreting Cells/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Cell Surface/genetics ; Signal Transduction
مستخلص: The regulation of pancreatic β cell mass is a critical factor to help maintain normoglycemia during insulin resistance. Nutrient-sensing G protein-coupled receptors (GPCR) contribute to aspects of β cell function, including regulation of β cell mass. Nutrients such as free fatty acids (FFAs) contribute to precise regulation of β cell mass by signaling through cognate GPCRs, and considerable evidence suggests that circulating FFAs promote β cell expansion by direct and indirect mechanisms. Free Fatty Acid Receptor 2 (FFA2) is a β cell-expressed GPCR that is activated by short chain fatty acids, particularly acetate. Recent studies of FFA2 suggest that it may act as a regulator of β cell function. Here, we set out to explore what role FFA2 may play in regulation of β cell mass. Interestingly, Ffar2(-/-) mice exhibit diminished β cell mass at birth and throughout adulthood, and increased β cell death at adolescent time points, suggesting a role for FFA2 in establishment and maintenance of β cell mass. Additionally, activation of FFA2 with Gαq/11-biased agonists substantially increased β cell proliferation in in vitro and ex vivo proliferation assays. Collectively, these data suggest that FFA2 may be a novel therapeutic target to stimulate β cell growth and proliferation.
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معلومات مُعتمدة: UC4 DK104166 United States DK NIDDK NIH HHS; F31 DK102371 United States DK NIDDK NIH HHS; T32 HD007502 United States HD NICHD NIH HHS; R01 DK104927 United States DK NIDDK NIH HHS; R01 DK060581 United States DK NIDDK NIH HHS; I01 BX000990 United States BX BLRD VA; P30 DK020595 United States DK NIDDK NIH HHS; IK2 BX001587 United States BX BLRD VA; T32 DK007169 United States DK NIDDK NIH HHS; R25 GM079300 United States GM NIGMS NIH HHS; T32 GM008061 United States GM NIGMS NIH HHS; UL1 TR001422 United States TR NCATS NIH HHS; P30 DK097512 United States DK NIDDK NIH HHS
المشرفين على المادة: 0 (Fatty Acids, Nonesterified)
0 (Fatty Acids, Volatile)
0 (Receptors, Cell Surface)
0 (free fatty acid 2 receptor, mouse)
تواريخ الأحداث: Date Created: 20160622 Date Completed: 20180430 Latest Revision: 20240216
رمز التحديث: 20240216
مُعرف محوري في PubMed: PMC4914960
DOI: 10.1038/srep28159
PMID: 27324831
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/srep28159