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The human glucagon receptor encoding gene: structure, cDNA sequence and chromosomal localization

S Lok1, J L Kuijper, L J Jelinek

  • 1Department of Molecular and Cellular Biology, ZymoGenetics Inc., Seattle, WA 95105.

Gene
|March 25, 1994
PubMed
Summary

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Researchers identified the human glucagon receptor gene (GGR), crucial for blood glucose regulation. This discovery advances understanding of diabetes pathogenesis and potential genetic links.

Area of Science:

  • Molecular Biology
  • Genetics
  • Endocrinology

Background:

  • The human glucagon receptor (GGR) gene is vital for understanding blood glucose regulation.
  • Identifying GGR may reveal genetic factors contributing to diabetes pathogenesis.

Purpose of the Study:

  • To isolate and characterize the complete functional human glucagon receptor (GGR) gene.
  • To determine the GGR gene's location on human chromosomes and analyze its genomic structure.

Main Methods:

  • cDNA isolation from a liver library using polymerase chain reaction and colony hybridization.
  • Functional characterization including [125I]glucagon binding and cyclic adenosine 3',5'-monophosphate signaling.
  • Southern blot analysis for gene locus identification and in situ hybridization for chromosomal mapping.

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  • Genomic sequence analysis to determine coding region size and intron-exon structure.

    • Main Results:

    • A cDNA encoding a functional human GGR was successfully isolated.
    • The human GGR protein shares 80% identity with its rat counterpart and binds glucagon.
    • Southern blot analysis confirmed a single GGR locus in the human genome.
    • In situ hybridization mapped the GGR locus to chromosome 17q25.
    • Genomic analysis revealed a 5.5 kb coding region interrupted by 12 introns.

    Conclusions:

    • The characterization of the human GGR gene provides a foundation for understanding glucoregulation.
    • The GGR gene's localization and structure offer insights into potential genetic bases for diabetes.
    • This research facilitates further studies into GGR function and its role in metabolic diseases.