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

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.
• 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.