Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard.
Glucagon-like peptide 1 stimulates insulin secretion and inhibits glucagon secretion, gastric emptying, and feeding, suggesting it may be biologically useful for the treatment of diabetes. A lizard glucagon-like peptide 1 (GLP-1)-related peptide, exendin 4, binds to the GLP-1 receptor and mimics the actions of GLP-1 in vivo. To determine the genetic relationship between exendin 4 and GLP-1, we analyzed the structure and expression of pancreatic and intestinal proglucagon mRNAs in the reptile Heloderma suspectum. Two different proglucagon cDNAs (lizard proglucagon I (LPI) and lizard proglucagon II (LPII)), with unique 3'-untranslated regions were identified. Two LPI mRNA transcripts, approximately 1.6 and 2.1 kilobases, encoded glucagon and GLP-1 but not GLP-2 and were restricted in expression to the pancreas. In contrast, a 1.1-kilobase LPII mRNA transcript, encoding glucagon, GLP-1, and GLP-2 utilized a different 3'-untranslated region and was expressed in both pancreas and intestine. Lizard proglucagon mRNA transcripts were not detectable by reverse transcription-polymerase chain reaction or Northern blotting in salivary gland. A single class of lizard salivary gland proexendin cDNAs encoded the sequence of exendin 4 and a 45-amino acid exendin NH2-terminal peptide. Exendin mRNA transcripts were expressed in the salivary gland, but not pancreas or intestine. These data demonstrate that GLP-1 and exendin 4 represent related yet distinct peptides encoded by different genes in the lizard.
Chen
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Department of Medicine, Banting and Best Diabetes Centre, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada M5G 2C4.
Drucker
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary; D000077270:Exenatide; D005786:Gene Expression Regulation; D005934:Glucagon / Q000235:genetics* / Q000378:metabolism; D008116:Lizards; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics*; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D012469:Salivary Glands / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014688:Venoms
D018076:DNA, Complementary; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D014688:Venoms; D052336:Proglucagon; D005934:Glucagon; D000077270:Exenatide