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Common variation in the sodium/glucose cotransporter 2 gene SLC5A2 does neither affect fasting nor glucose-suppressed plasma glucagon concentrations.

التفاصيل البيبلوغرافية
العنوان: Common variation in the sodium/glucose cotransporter 2 gene SLC5A2 does neither affect fasting nor glucose-suppressed plasma glucagon concentrations.
المؤلفون: Ordelheide AM; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; German Center for Diabetes Research (DZD), Otfried-Müller-Straße 10, Tübingen, Germany., Böhm A; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; German Center for Diabetes Research (DZD), Otfried-Müller-Straße 10, Tübingen, Germany.; Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany., Kempe-Teufel D; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; German Center for Diabetes Research (DZD), Otfried-Müller-Straße 10, Tübingen, Germany.; Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany., Wagner R; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; German Center for Diabetes Research (DZD), Otfried-Müller-Straße 10, Tübingen, Germany.; Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany., Machicao F; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; German Center for Diabetes Research (DZD), Otfried-Müller-Straße 10, Tübingen, Germany.; Institute of Experimental Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg, Germany., Heni M; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; German Center for Diabetes Research (DZD), Otfried-Müller-Straße 10, Tübingen, Germany.; Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany., Stefan N; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; German Center for Diabetes Research (DZD), Otfried-Müller-Straße 10, Tübingen, Germany.; Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany., Fritsche A; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; German Center for Diabetes Research (DZD), Otfried-Müller-Straße 10, Tübingen, Germany.; Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; Division of Nutritional and Preventive Medicine, Department of Internal Medicine, University Hospital Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany., Häring HU; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; German Center for Diabetes Research (DZD), Otfried-Müller-Straße 10, Tübingen, Germany.; Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; Interfaculty Center for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen, Germany., Staiger H; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Otfried-Müller-Straße 10, Tübingen, Germany.; German Center for Diabetes Research (DZD), Otfried-Müller-Straße 10, Tübingen, Germany.; Institute of Experimental Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, Ingolstädter Landstraße 1, Neuherberg, Germany.; Interfaculty Center for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen, Germany.; Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen, Germany.
المصدر: PloS one [PLoS One] 2017 May 04; Vol. 12 (5), pp. e0177148. Date of Electronic Publication: 2017 May 04 (Print Publication: 2017).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Fasting*, Glucagon/*blood , Glucose/*administration & dosage , Sodium-Glucose Transporter 2/*genetics, Adult ; Blood Glucose/analysis ; Female ; Glucose Tolerance Test ; Humans ; Insulin/blood ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors
مستخلص: Aim: Inhibition of sodium/glucose cotransporter 2 (SGLT2), the key transport protein in renal glucose reabsorption, promotes glucose excretion and represents a new concept in the therapy of type-2 diabetes. In addition, SGLT2 inhibition elevates circulating glucagon concentrations and enhances hepatic glucose production. Since SGLT2 is expressed in human pancreatic α-cells and regulates glucagon release, we tested whether common variants of the SGLT2 gene SLC5A2 associate with altered plasma glucagon concentrations in the fasting state and upon glucose challenge.
Methods: A study population of 375 healthy subjects at increased risk for type-2 diabetes, phenotyped by a 5-point oral glucose tolerance test (OGTT) and genotyped for recently described SLC5A2 tagging single nucleotide polymorphisms (SNPs), was selected for plasma glucagon measurements.
Results: After adjustment for gender, age, body mass index, and insulin sensitivity, the four tagging SNPs (rs9924771, rs3116150, rs3813008, rs9934336), tested separately or as genetic score, were neither significantly nor nominally associated with plasma glucagon concentrations at any time during the OGTT, with the inverse AUC of glucagon or the glucagon fold-change during the OGTT (p ≥ 0.2, all). Testing for genotype-related differences in the time course of the glucagon response using MANOVA did also not reveal any significant or nominal associations (p ≥ 0.5, all).
Conclusion: We could not obtain statistically significant evidence for a role of common SLC5A2 variants in the regulation of glucagon release in the fasting state or upon glucose challenge. Moreover, the reported nominal effects of individual SLC5A2 variants on fasting and post-challenge glucose levels may probably not be mediated by altered glucagon release.
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المشرفين على المادة: 0 (Blood Glucose)
0 (Insulin)
0 (SLC5A2 protein, human)
0 (Sodium-Glucose Transporter 2)
9007-92-5 (Glucagon)
IY9XDZ35W2 (Glucose)
تواريخ الأحداث: Date Created: 20170505 Date Completed: 20170915 Latest Revision: 20181113
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC5417681
DOI: 10.1371/journal.pone.0177148
PMID: 28472182
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0177148