Glucagon receptor gene mutations with hyperglucagonemia but without the glucagonoma syndrome

Figure 1 Islet from patient. Immunohistochemistry for A: Insulin; B: Glucagon, x 200 magnification (600 μm at maximum diameter).

Figure 2 Genetic findings. A: Sequencing results showing a heterozygous 33 nucleotide deletion and 5 point mutations in exon 11 of the GCGR; B: Amino acid sequence showing K349_G359del, E362K, V368L, K381E, S389N in the GCGR. Alignments done using Clustal W multiple sequence alignments software[25]. Numbers indicate the position of the last residue shown along the GCGR cDNA/protein.

Figure 3 Membrane topology prediction. The loss of 11 amino acids from the glucagon receptor (GCGR) 6^th transmembrane domain is predicted to prevent the insertion of GCGR into the plasma membrane. A: Predicted normal GCGR membrane topology; B: Predicted K349_G359del GCGR membrane topology. Software used: Meta^TM[22]; input amino acid sequence shown in Figure 2B. DAS: Distributed Annotation System.