Proglucagon processing in porcine and human pancreas
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Proglucagon processing in porcine and human pancreas. / Holst, J J; Bersani, M; Johnsen, A H; Kofod, Hans; Hartmann, B; Orskov, C.
I: Journal of Biological Chemistry, Bind 269, Nr. 29, 1994, s. 18827-33.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Proglucagon processing in porcine and human pancreas
AU - Holst, J J
AU - Bersani, M
AU - Johnsen, A H
AU - Kofod, Hans
AU - Hartmann, B
AU - Orskov, C
PY - 1994
Y1 - 1994
N2 - In the pancreas proglucagon (PG), a peptide precursor of 160 amino acids is cleaved to produce glucagon and a 30-amino acid N-terminal flanking peptide, but the fate of the C-terminal flanking peptide (99 amino acids) is incompletely known. We subjected acid ethanol extracts of human and porcine pancreases to gel filtration and analyzed the fractions with specific radioimmunoassays for the following regions of proglucagon: PG 62-69, PG 72-81, PG 78-87, PG 98-107 amide, PG 126-134, and PG 149-158. Based on these assays and successive purifications by high performance liquid chromatography we isolated and purified to homogeneity three porcine peptides which were subjected to mass spectrometry and sequencing. One peptide was PG 64-69. The second was PG 72-108, as determined by mass spectrometry, N-terminal amino acid sequencing, and specific radioimmunoassays. The third had a molecular size of approximately 10,000, an N-terminal sequence corresponding to PG 72-81, and a C-terminal sequence terminating at PG 158 (specific radioimmunoassay). A similar peptide with an identical N-terminal sequence, a C-terminal sequence corresponding to PG 146-158, and a molecular mass of 9969 (theoretical mass for human PG 72-158 = 9971) was isolated from human pancreas together with small amounts of a peptide corresponding to PG 72-107 amide. Thus, the pancreatic processing of the C-terminal flanking peptide in proglucagon includes the formation of equimolar (to glucagon) amounts of PG 64-69 and PG 72-158 (major proglucagon fragment) and smaller amounts of N-terminally extended glucagon-like peptide-1 (GLP-1) (PG 72-108 in pigs and PG 72-107 amide in humans).
AB - In the pancreas proglucagon (PG), a peptide precursor of 160 amino acids is cleaved to produce glucagon and a 30-amino acid N-terminal flanking peptide, but the fate of the C-terminal flanking peptide (99 amino acids) is incompletely known. We subjected acid ethanol extracts of human and porcine pancreases to gel filtration and analyzed the fractions with specific radioimmunoassays for the following regions of proglucagon: PG 62-69, PG 72-81, PG 78-87, PG 98-107 amide, PG 126-134, and PG 149-158. Based on these assays and successive purifications by high performance liquid chromatography we isolated and purified to homogeneity three porcine peptides which were subjected to mass spectrometry and sequencing. One peptide was PG 64-69. The second was PG 72-108, as determined by mass spectrometry, N-terminal amino acid sequencing, and specific radioimmunoassays. The third had a molecular size of approximately 10,000, an N-terminal sequence corresponding to PG 72-81, and a C-terminal sequence terminating at PG 158 (specific radioimmunoassay). A similar peptide with an identical N-terminal sequence, a C-terminal sequence corresponding to PG 146-158, and a molecular mass of 9969 (theoretical mass for human PG 72-158 = 9971) was isolated from human pancreas together with small amounts of a peptide corresponding to PG 72-107 amide. Thus, the pancreatic processing of the C-terminal flanking peptide in proglucagon includes the formation of equimolar (to glucagon) amounts of PG 64-69 and PG 72-158 (major proglucagon fragment) and smaller amounts of N-terminally extended glucagon-like peptide-1 (GLP-1) (PG 72-108 in pigs and PG 72-107 amide in humans).
KW - Amino Acid Sequence
KW - Animals
KW - Glicentin
KW - Glucagon
KW - Glucagon-Like Peptides
KW - Humans
KW - Molecular Sequence Data
KW - Pancreas
KW - Peptide Fragments
KW - Proglucagon
KW - Protein Precursors
KW - Protein Processing, Post-Translational
KW - Swine
M3 - Journal article
C2 - 8034635
VL - 269
SP - 18827
EP - 18833
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 29
ER -
ID: 243108