A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro
| العنوان: | A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro |
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| المؤلفون: | Yoshifumi Suzuki, Yoshiharu Tokuyama, Akira Tohgo, Fumio Shimada, Hideichi Makino, Fumiko Ikehata, Azuma Kanatsuka, Kazuo Yagui, Yasushi Saito, Shin Takasawa, Hiroshi Okamoto, M. Mimura, Naotake Hashimoto, Koji Nata |
| المصدر: | Diabetologia. 41:1024-1028 |
| بيانات النشر: | Springer Science and Business Media LLC, 1998. |
| سنة النشر: | 1998 |
| مصطلحات موضوعية: | Male, ADP-ribosyl Cyclase, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Mutation, Missense, In Vitro Techniques, CD38, Impaired glucose tolerance, Exon, NAD+ Nucleosidase, Gene Frequency, Japan, Antigens, CD, Multienzyme Complexes, Internal medicine, Insulin Secretion, Internal Medicine, medicine, Animals, Humans, Insulin, Missense mutation, Polymorphism, Single-Stranded Conformational, Membrane Glycoproteins, biology, Exons, Middle Aged, medicine.disease, ADP-ribosyl Cyclase 1, Antigens, Differentiation, Endocrinology, Amino Acid Substitution, Diabetes Mellitus, Type 2, COS Cells, Mutagenesis, Site-Directed, biology.protein, GLUT2, Female, Beta cell |
| الوصف: | Cyclic adenosine 5′diphosphate-ribose (cADPR) is thought to have a second messenger role in insulin secretion through mobilisation of Ca2 +. As human lymphocyte antigen CD38 has both ADP-ribosyl cyclase and cADPR hydrolase activity, it may be important in glucose-induced insulin secretion in islets. Thirty one randomly selected Japanese patients with Type II diabetes mellitus who had first-degree and/or second-degree relative(s) with Type II diabetes mellitus were screened for mutations of this gene using single-stranded conformation polymorphism. Two variant patterns in exon 3 and exon 4 of the CD38 gene were identified. The variant in exon 3 resulted in an amino acid substitution from Arg140 (CGG) to Trp (TGG). The Arg140Trp mutation was observed in 4 of 31 patients, and allele frequencies were significantly different in patients and the control subjects (p = 0.004). One patient with this mutation has two missense mutations on beta cell/liver glucose transporter (GLUT2) gene; her mother, who has impaired glucose tolerance, also has this mutation on the CD38 gene and one missense mutation on the GLUT2 gene. Enzyme activity studies using COS-7 cells expressing the Arg140Trp mutation showed a reduction in ADP-ribosyl cyclase and cADPR hydrolase activity of around 50 %. The Arg140Trp mutation on CD38 thus appears to contribute to the development of Type II diabetes mellitus via the impairment of glucose-induced insulin secretion in the presence of other genetic defects. [Diabetologia (1998) 41: 1024–1028] |
| تدمد: | 1432-0428 0012-186X |
| DOI: | 10.1007/s001250051026 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77b352c3272616c4c19c6d07067274eb https://doi.org/10.1007/s001250051026 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....77b352c3272616c4c19c6d07067274eb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320428 0012186X |
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| DOI: | 10.1007/s001250051026 |