A 3-basepair in-frame deletion (delta Leu999) in exon 17 of the insulin receptor gene in a family with insulin resistance
| Autor: | Masato Kasuga, Yasuhiko Iwamoto, K Momomura, Masato Odawara, Yoshihiko Takahashi, C Matsumoto, Takuya Awata, Takashi Kadowaki |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Adult
Male medicine.medical_specialty Herpesvirus 4 Human Adolescent Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Molecular Sequence Data Gene mutation Transfection Biochemistry Exon Endocrinology Insulin resistance Japan Leucine Internal medicine medicine Hyperinsulinemia Humans Insulin Acanthosis Nigricans Lymphocytes Phosphorylation Child Cell Line Transformed biology Base Sequence Biochemistry (medical) Autophosphorylation Exons Glucose Tolerance Test medicine.disease Receptor Insulin Insulin receptor biology.protein Female Insulin Resistance Hyperinsulinism Gene Deletion |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 79(6) |
| ISSN: | 0021-972X |
| Popis: | We studied a woman with acanthosis nigricans and insulin resistance. The patient's Epstein-Barr virus-transformed lymphocytes revealed slightly decreased insulin binding and markedly decreased insulin-stimulated autophosphorylation of the insulin receptor. The nucleotide sequence analysis of the patient's genomic DNA revealed a 3-basepair in-frame deletion in one allele, resulting in the loss of leucine at position 999 of the insulin receptor (delta Leu999). The messenger ribonucleic acid transcripts from the mutant allele in the patient's lymphocytes were not decreased. Insulin-stimulated autophosphorylation of the insulin receptor from cells expressing delta Leu999 mutant insulin receptor complementary DNA was markedly decreased. The proband, her mother, elder brother, and younger brother, who were heterozygous for this mutation, showed moderate or marked hyperinsulinemia during oral glucose tolerance tests. Although fasting glucose levels were normal and fasting insulin values were preserved in all subjects with the mutation for the 8-yr period of observation, a tendency of progressive increase in postload glucose levels was observed. These results suggest that the delta Leu999 mutation, which reduces tyrosine kinase activity, was responsible for insulin resistance and contributed to postload hyperglycemia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|