A 3-basepair in-frame deletion ({Delta}Leu{sup 999}) in exon 17 of the insulin receptor gene in a family with insulin resistance
Journal Article
·
· Journal of Clinical Endocrinology and Metabolism
- Jichi Medical School, Tochigi (Japan); and others
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 of one allele, resulting in the loss of leucine at position 999 of the insulin receptor ({Delta}Leu{sup 999}). 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}Leu{sup 999} 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 tendancy of progressive increase in postload glucose levels were observed. These results suggest that the {Delta}Leu{sup 999} mutation, which reduces tyrosine kinase activity, was responsible for insulin resistance and contributed to postload hyperglycemia. 27 refs., 3 figs., 1 tab.
- OSTI ID:
- 183230
- Journal Information:
- Journal of Clinical Endocrinology and Metabolism, Journal Name: Journal of Clinical Endocrinology and Metabolism Journal Issue: 6 Vol. 79; ISSN JCEMAZ; ISSN 0021-972X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Deletion of exon 3 of the insulin receptor gene in a kindred with a familial form of insulin resistance
A nonsense mutation causing decreased levels of insulin receptor mRNA: Detection by a simplified technique for direct sequencing of genomic DNA amplified by the polymerase chain reaction
Monoclonal antibodies to the human insulin receptor that activate glucose transport but not insulin receptor kinase activity
Journal Article
·
Sun May 01 00:00:00 EDT 1994
· Journal of Clinical Endocrinology and Metabolism
·
OSTI ID:450611
A nonsense mutation causing decreased levels of insulin receptor mRNA: Detection by a simplified technique for direct sequencing of genomic DNA amplified by the polymerase chain reaction
Journal Article
·
Sun Dec 31 23:00:00 EST 1989
· Proceedings of the National Academy of Sciences of the United States of America; (USA)
·
OSTI ID:7063781
Monoclonal antibodies to the human insulin receptor that activate glucose transport but not insulin receptor kinase activity
Journal Article
·
Fri May 01 00:00:00 EDT 1987
· Proc. Natl. Acad. Sci. U.S.A.; (United States)
·
OSTI ID:5514949