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Evaluation of a rare glucose-dependent insulinotropic polypeptide receptor variant in a patient with diabetes.

التفاصيل البيبلوغرافية
العنوان: Evaluation of a rare glucose-dependent insulinotropic polypeptide receptor variant in a patient with diabetes.
المؤلفون: Jacobi SF; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Institute of Experimental Pediatric Endocrinology, Berlin, Germany.; University Heart Center Freiburg-Bad Krozingen, Department of Congenital Heart Disease and Pediatric Cardiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Khajavi N; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Institute of Experimental Pediatric Endocrinology, Berlin, Germany., Kleinau G; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Institute of Experimental Pediatric Endocrinology, Berlin, Germany.; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Institut für Medizinische Physik und Biophysik, Group Protein X-ray Crystallography and Signal Transduction, Berlin, Germany., Teumer A; Department SHIP/Clinical-Epidemiological Research, Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany., Scheerer P; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Institut für Medizinische Physik und Biophysik, Group Protein X-ray Crystallography and Signal Transduction, Berlin, Germany., Homuth G; Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine, University Greifswald, Greifswald, Germany., Völzke H; Department SHIP/Clinical-Epidemiological Research, Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.; German Center for Diabetes Research (DZD), Site Greifswald, Greifswald, Germany., Wiegand S; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Institute of Experimental Pediatric Endocrinology, Berlin, Germany., Kühnen P; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Institute of Experimental Pediatric Endocrinology, Berlin, Germany., Krude H; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Institute of Experimental Pediatric Endocrinology, Berlin, Germany., Gong M; Experimental and Clinical Research Center (ECRC), a joint collaboration of Charité and Max-Delbrück-Center of Molecular Medicine, Berlin, Germany., Raile K; Experimental and Clinical Research Center (ECRC), a joint collaboration of Charité and Max-Delbrück-Center of Molecular Medicine, Berlin, Germany.; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Department of Paediatric Endocrinology and Diabetology, Berlin, Germany., Biebermann H; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Institute of Experimental Pediatric Endocrinology, Berlin, Germany.
المصدر: Diabetes, obesity & metabolism [Diabetes Obes Metab] 2019 May; Vol. 21 (5), pp. 1168-1176. Date of Electronic Publication: 2019 Feb 19.
نوع المنشور: Case Reports; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 100883645 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1463-1326 (Electronic) Linking ISSN: 14628902 NLM ISO Abbreviation: Diabetes Obes Metab Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford : Wiley-Blackwell, c1999-
مواضيع طبية MeSH: Polymorphism, Single Nucleotide*, Diabetes Mellitus, Type 2/*genetics , Receptors, Gastrointestinal Hormone/*genetics, Adolescent ; Age of Onset ; Amino Acid Substitution/genetics ; Animals ; Arginine/genetics ; COS Cells ; Child ; Chlorocebus aethiops ; Cohort Studies ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/metabolism ; Female ; Gene Frequency ; Genome-Wide Association Study ; Germany/epidemiology ; Homozygote ; Humans ; Insulin Resistance/genetics ; Leucine/genetics ; Male ; Pediatric Obesity/complications ; Pediatric Obesity/epidemiology ; Pediatric Obesity/genetics
مستخلص: Aims: Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that augments insulin secretion in pancreatic β-cells via its glucose-dependent insulinotropic polypeptide receptor (GIPR). Recent genome-wide association studies identified a single nucleotide variant (SNV) in the GIPR encoding gene (GIPR), rs1800437, that is associated with obesity and insulin resistance. In the present study, we tested whether GIPR variants contribute to obesity and disturb glucose homeostasis or diabetes in specific patient populations.
Materials and Methods: Exon sequencing of GIPR was performed in 164 children with obesity and insulin resistance and in 80 children with paediatric-onset diabetes of unknown origin. The Study of Health in Pomerania (SHIP) cohort, comprising 8320 adults, was screened for the GIPR variant Arg217Leu. GIPR variants were expressed in COS-7 cells and cAMP production was measured upon stimulation with GIP. Cell surface expression was determined by ELISA. Protein homology modelling of the GIPR variants was performed to extract three-dimensional information of the receptor.
Results: A heterozygous missense GIPR variant Arg217Leu (rs200485112) was identified in a patient of Asian ancestry. Functional characterization of Arg217Leu revealed reduced surface expression and signalling after GIP challenge. The homology model of the GIPR structure supports the observed functional relevance of Arg217Leu.
Conclusion: In vitro functional studies and protein homology modelling indicate a potential relevance of the GIPR variant Arg217Leu in receptor function. The heterozygous variant displayed partial co-segregation with diabetes. Based on these findings, we suggest that GIPR variants may play a role in disturbed glucose homeostasis and may be of clinical relevance in homozygous patients.
(© 2019 John Wiley & Sons Ltd.)
فهرسة مساهمة: Keywords: GIPR variants; diabetes; glucose homeostasis; glucose-dependent insulinotropic polypeptide receptor (GIPR); incretin; insulin resistance; obesity
المشرفين على المادة: 0 (Receptors, Gastrointestinal Hormone)
94ZLA3W45F (Arginine)
D6H00MV7K8 (gastric inhibitory polypeptide receptor)
GMW67QNF9C (Leucine)
تواريخ الأحداث: Date Created: 20190221 Date Completed: 20200330 Latest Revision: 20200330
رمز التحديث: 20231215
DOI: 10.1111/dom.13634
PMID: 30784161
قاعدة البيانات: MEDLINE
الوصف
تدمد:1463-1326
DOI:10.1111/dom.13634