Hamster preproglucagon contains the sequence of glucagon and two related peptides

Abstract

Glucagon is a 29-amino acid polypeptide hormone synthesized by the A cells of the endocrine pancreas. Its primary site of action is the liver where it stimulates glycogenolysis, gluconeogenesis and ketogenesis. In mammals, biosynthetic studies have shown that glucagon is derived from a precursor of molecular weight (Mr) approximately 18,000 which is five to six times larger than glucagon. Glucagon-containing polypeptides and immunoreactants of various sizes have also been described from stomach, intestine, brain and salivary gland. Here, we have determined the structure of hamster pancreatic preproglucagon from the sequence of its cDNA. This 180-amino acid precursor contains the sequence of glucagon and two glucagon-like polypeptides arranged in tandem. The precursor also contains the sequences of several non-pancreatic glucagon-containing polypeptides which suggests that, in mammals, both pancreatic and non-pancreatic glucagon and glucagon-containing polypeptides may be derived from a common precursor by tissue-specific processing. We have tentatively identified each of the glucagon-like immunoreactants which have been described with respect to the sequence of proglucagon and have proposed a scheme for the processing of pancreatic proglucagon.

Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005

“…This molecule contained a glucagon-like peptide (GLP) in addition to anglerfish glucagon, and therefore nurtured the notion that the proglucagon gene might encode more than one bioactive peptide. Finally, in 1983, G. Bell and co-workers cloned the hamster and human proglucagon genes [18,19] and were thereby able to deduce the human proglucagon sequence. In agreement with the prediction, its N-terminus consisted of the full sequence of glicentin, containing also the glucagon sequence.…”

Isolation and characterisation of GLP‐1 7–36 amide from rat intestine Elevated levels in diabetic rats

“…As well as for glucagon, it also encodes for two glucagon-like peptides (GLP-1 1-37 or proglucagon sequence 72-108, and GLP-2 or proglucagon sequence 126-158) [3]. Paired basic amino acids were considered to be the enzymatic cleavage points.…”

Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets

“…Glucagon-like peptide-2 has no effect on insulin secretion at any glucose concentration tested. It is concluded that glucagon-like peptide-t, in contrast to glucagon-like peptide-2, exhibits a glucose-dependent insulinotropic action on isolated rat pancreatic islets similar to that of glucagon and gastric inhibitory polypeptide.Key words: Glucagon-like peptide-t, glucagon-like peptide-2, insulin release, glucose dependency, isolated islets.Pancreatic preproglucagon m-RNA, the precursor of pancreatic glucagon, has been cloned and sequenced from different species using recombinant DNA-techniques [1][2][3][4][5]. Two other peptides have been found arranged in tandem on the same m-RNA in close proximity C-terminal to the glucagon precursor: glucagonlike peptide-I (GLP-1) and glucagon-like peptide-2 (GLP-2) comprising 36 and 34 amino acid residues, respectively.…”

“…Pancreatic preproglucagon m-RNA, the precursor of pancreatic glucagon, has been cloned and sequenced from different species using recombinant DNA-techniques [1][2][3][4][5]. Two other peptides have been found arranged in tandem on the same m-RNA in close proximity C-terminal to the glucagon precursor: glucagonlike peptide-I (GLP-1) and glucagon-like peptide-2 (GLP-2) comprising 36 and 34 amino acid residues, respectively.…”