Human GLUT4/muscle-fat glucose-transporter gene

Characterization and genetic variation

John B. Buse, Kazuki Yasuda, Tracy P. Lay, Tracy S. Seo, Ann Louise Olson, Jeffrey E. Pessin, John H. Karam, Susumu Seino, Graeme I. Bell

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Four overlapping DNA fragments spanning 32 kb containing the human GLUT4 facilitative glucose-transporter gene were isolated and characterized. The sequence of the GLUT4 gene (∼6.3 kb) and 2.0 kb of the promoter region was determined. The sequence of the promoter revealed potential binding sites for transcription factors known to regulate gene expression in muscle cells and adipocytes. However, transfection of constructs including 2 kb of the GLUT4 promoter fused to the bacterial CAT gene into 3T3-L1 adipocytes displayed only weak promoter activity. Because insulin resistance plays a prominent role in the development of NIDDM, genetic variation in the sequence of GLUT4 also was evaluated. Oligonucleotide primer pairs were selected that allowed the protein-coding region of the human GLUT4 gene to be amplified by PCR. The sequence of the protein-coding region of the GLUT4 gene and all intron-exon junctions was determined for a single diabetic Pima Indian and was identical to that of the cloned gene and cDNA. SSCP analysis was used to screen patients with diabetes mellitus and normal, healthy nondiabetic individuals for mutations at the GLUT4 locus. In addition to the silent substitution in the codon for Asn130 (AAC or AAT) and a Val383(GTC)→lle(ATC) replacement described previously, two new variants were identified. One was a T→A substitution in intron 1 that was found In 1 of 36 NIDDM patients who were typed for this variant. The second was a IIe385(ATT)→Thr(ACT) replacement that occurred in 1 normal individual and was not found in any of 676 other normal and diabetic subjects. A large and racially diverse group of normal and diabetic individuals also was screened for the IIe383 polymorphism. It occurred in both diabetic and nondiabetic subjects. There is no indication from our data that these polymorphisms are associated with NIDDM.

Original languageEnglish (US)
Pages (from-to)1436-1445
Number of pages10
JournalDiabetes
Volume41
Issue number11
StatePublished - Nov 1992
Externally publishedYes

Fingerprint

Facilitative Glucose Transport Proteins
Fats
Muscles
Type 2 Diabetes Mellitus
Genes
Adipocytes
Introns
Open Reading Frames
Potassium Iodide
Bacterial Genes
Single-Stranded Conformational Polymorphism
DNA Primers
Genetic Promoter Regions
Codon
Muscle Cells
Transfection
Insulin Resistance
Exons
Diabetes Mellitus
Transcription Factors

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Buse, J. B., Yasuda, K., Lay, T. P., Seo, T. S., Olson, A. L., Pessin, J. E., ... Bell, G. I. (1992). Human GLUT4/muscle-fat glucose-transporter gene: Characterization and genetic variation. Diabetes, 41(11), 1436-1445.

Human GLUT4/muscle-fat glucose-transporter gene : Characterization and genetic variation. / Buse, John B.; Yasuda, Kazuki; Lay, Tracy P.; Seo, Tracy S.; Olson, Ann Louise; Pessin, Jeffrey E.; Karam, John H.; Seino, Susumu; Bell, Graeme I.

In: Diabetes, Vol. 41, No. 11, 11.1992, p. 1436-1445.

Research output: Contribution to journalArticle

Buse, JB, Yasuda, K, Lay, TP, Seo, TS, Olson, AL, Pessin, JE, Karam, JH, Seino, S & Bell, GI 1992, 'Human GLUT4/muscle-fat glucose-transporter gene: Characterization and genetic variation', Diabetes, vol. 41, no. 11, pp. 1436-1445.
Buse JB, Yasuda K, Lay TP, Seo TS, Olson AL, Pessin JE et al. Human GLUT4/muscle-fat glucose-transporter gene: Characterization and genetic variation. Diabetes. 1992 Nov;41(11):1436-1445.
Buse, John B. ; Yasuda, Kazuki ; Lay, Tracy P. ; Seo, Tracy S. ; Olson, Ann Louise ; Pessin, Jeffrey E. ; Karam, John H. ; Seino, Susumu ; Bell, Graeme I. / Human GLUT4/muscle-fat glucose-transporter gene : Characterization and genetic variation. In: Diabetes. 1992 ; Vol. 41, No. 11. pp. 1436-1445.
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