The acute insulin response (AIR), a measure of pancreatic β-cell function, aggregates in families and is a predictor for the development of non-insulin-dependent diabetes mellitus (NIDDM) in insulin-resistant Pima Indians. To assess the genetic components of AIR and NIDDM, polymorphic dinucleotide repeat regions in two candidate genes, the liver/islet glucose transporter gene (GLUT2) and the glucokinase gene, were evaluated. Sib-pair linkage analyses were performed to determine if linkage exists between these marker loci and measurements of AIR and NIDDM. No linkage was found between glucokinase and either AIR or NIDDM. Robust sib-pair linkage analyses suggest linkage between GLUT2 and acute insulin response (P = 0.04), but no linkage was observed with NIDDM. The coding region of the GLUT2 gene was screened for mutations using polymerase chain reaction-single-strand conformation polymorphism analysis. A single base change was identified in exon 3 in ∼5% of the study population, and it constitutes the first reported mutation in the human GLUT2 gene. This base change resulted in an amino acid substitution (Thr110→Ile110) in the second membrane-spanning region of the GLUT2 protein. No significant association was noted between AIR and the presence or absence of the mutation. Thus, this mutation in GLUT2 is unlikely the cause of a low AIR in Pima Indians.
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Original Contributions|
April 01 1994
Linkage Analysis of Acute Insulin Secretion With GLUT2 and Glucokinase in Pima Indians and the Identification of a Missense Mutation in GLUT2
Rachel C Janssen;
Rachel C Janssen
Department of Zoology, Arizona State University
Tempe, Arizona
Clinical Diabetes and Nutrition and Diabetes and Arthritis Epidemiology Sections, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Phoenix, Arizona
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Clifton Bogardus;
Clifton Bogardus
Clinical Diabetes and Nutrition and Diabetes and Arthritis Epidemiology Sections, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Phoenix, Arizona
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Jun Takeda;
Jun Takeda
Howard Hughes Medical Institute and the Department of Biochemistry and Molecular Biology, University of Chicago
Chicago, Illinois
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William C Knowler;
William C Knowler
Clinical Diabetes and Nutrition and Diabetes and Arthritis Epidemiology Sections, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Phoenix, Arizona
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D Bruce Thompson
D Bruce Thompson
Clinical Diabetes and Nutrition and Diabetes and Arthritis Epidemiology Sections, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
Phoenix, Arizona
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Address correspondence to Dr. D. Bruce Thompson, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 4212 North 16th Street, Phoenix, AZ 85016.
Diabetes 1994;43(4):558–563
Article history
Received:
July 09 1993
Revision Received:
December 09 1993
Accepted:
December 09 1993
PubMed:
8138061
Citation
Rachel C Janssen, Clifton Bogardus, Jun Takeda, William C Knowler, D Bruce Thompson; Linkage Analysis of Acute Insulin Secretion With GLUT2 and Glucokinase in Pima Indians and the Identification of a Missense Mutation in GLUT2. Diabetes 1 April 1994; 43 (4): 558–563. https://doi.org/10.2337/diab.43.4.558
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