Normal Insulin-Receptor cDNA Sequence in Pima Indians With NIDDM
Abstract
Pima Indians have served as a model of non-insulin-dependent diabetes mellitus (NIDDM). Within this population, inherited insulin resistance is a primary determinant of abnormal glucose metabolism. The insulin receptor is regarded as a “candidate gene” that could potentially be defective in Pima Indians or other populations with NIDDM. To directly address the question of potential insulin-receptor genetic defects in Pima Indians, we isolated and sequenced insulin-receptor cDNA from two Pima Indians with NIDDM. Small amounts of lymphoblast RNA were used to generate first-strand cDNA, which was then amplified via the polymerase chain reaction (PCR). In this way, seven overlapping segments of insulin-receptor cDNA were obtained. With the exception of the alternatively spliced 36-base pair exon 11, which is not expressed in lymphoblasts, the complete coding region of the mature proreceptor was examined with a combination of direct sequencing and sequencing of subcloned PCR segments. The nucleotide sequence in both subjects was identical to previously published insulin-receptor cDNA sequences obtained from healthy subjects. These data indicate that abnormalities of insulin binding and receptor function that have been previously observed in vitro with fresh and cultured cells from Pima Indians may be consequences of the diabetic milieu and/or genetic abnormalities in molecules that interact with the insulin receptor.
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With very rare exceptions, physiologically significant mutations in the insulin receptor gene have not been observed in type 2 diabetic patients from diverse ethnic populations.
“The insulin receptor gene, however, has been sequenced in a large number of type 2 diabetic patients from diverse ethnic populations and, with very rare exceptions, physiologically significant mutations in the insulin receptor gene have not been observed [159, 160].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [159]
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- Authors
- Moller, D. E., Yokota, A., & Flier, J. S.
- Affiliations
- Harvard University (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1989-11-01
- Volume
- 38
- Issue
- 11
- Pages
- 1496-1500
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2112967320
- Cited by
- 76
- References
- 30
- Citations by year
- 2026: 1 · 2018: 2 · 2015: 1 · 2013: 1 · 2012: 1
- FWCI
- 9.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK 28082-07)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- insulin receptor, Pima Indians, type 2 diabetes, insulin resistance, insulin receptor gene, cDNA sequence, lymphoblasts, genetic disorders, candidate genes
- MeSH terms
- Arizona, Base Sequence, Diabetes Mellitus, Type 2, DNA, Female, Gene Amplification, Humans, Indians, North American, Insulin Resistance, Male, Receptor, Insulin, Polymerase Chain Reaction
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