Effect of carboxypeptidase E deficiency on progastrin processing and gastrin messenger ribonucleic acid expression in mice with the fat mutation

V. Udupi, P. Gomez, L. Song, Oleg Varlamov, J. T. Reed, E. H. Leiter, L. D. Fricker, Jr Greeley G.H.

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Proforms of gastrointestinal peptides are cleaved at paired basic residues into intermediate forms. Paired basic residues at the C-terminal then are excised by carboxypeptidases before the peptide is amidated. An obese mouse, called Cpe(fat)/Cpe(fat), has a missense mutation in carboxypeptidase E (CPE) with no pancreatic CPE activity and a reduced processing of pancreatic proinsulin to insulin. The purpose of this study was 1) to look for the presence of CPE in the antrum of the stomach, duodenum, and colon in the Cpe(fat)/Cpe(fat) mouse; 2) to determine whether CPE is involved in the processing of progastrin (Pro-G) to its carboxyl-terminal amidated form; and 3) to determine whether a decrease in amidated gastrin results in an upregulation of stomach gastrin messenger RNA (mRNA) levels. In Cpe(fat)/Cpe(fat) mice, CPE activity was absent in the antrum and colon. In Cpe(fat)/Cpe(fat) mice, amidated gastrin levels were reduced significantly. Levels of the precursor for amidated gastrin (gastrin-Gly-Arg-Arg) were markedly elevated. Gastrin mRNA levels were increased approximately 2-fold over the levels in Cpe(fat)t/Cpe(fat) mice. These results indicate that CPE is needed for processing progastrin to gastrin in the stomach and that amidated gastrin exerts an inhibitory feedback effect on gastrin mRNA levels.

Original languageEnglish (US)
Pages (from-to)1959-1963
Number of pages5
JournalEndocrinology
Volume138
Issue number5
StatePublished - 1997
Externally publishedYes

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Carboxypeptidase H
Gastrins
Fats
RNA
Mutation
Stomach
Messenger RNA
Colon
big gastrin
Carboxypeptidases
Proinsulin
Obese Mice
Peptides
Missense Mutation
Duodenum

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Effect of carboxypeptidase E deficiency on progastrin processing and gastrin messenger ribonucleic acid expression in mice with the fat mutation. / Udupi, V.; Gomez, P.; Song, L.; Varlamov, Oleg; Reed, J. T.; Leiter, E. H.; Fricker, L. D.; Greeley G.H., Jr.

In: Endocrinology, Vol. 138, No. 5, 1997, p. 1959-1963.

Research output: Contribution to journalArticle

Udupi, V, Gomez, P, Song, L, Varlamov, O, Reed, JT, Leiter, EH, Fricker, LD & Greeley G.H., J 1997, 'Effect of carboxypeptidase E deficiency on progastrin processing and gastrin messenger ribonucleic acid expression in mice with the fat mutation', Endocrinology, vol. 138, no. 5, pp. 1959-1963.
Udupi, V. ; Gomez, P. ; Song, L. ; Varlamov, Oleg ; Reed, J. T. ; Leiter, E. H. ; Fricker, L. D. ; Greeley G.H., Jr. / Effect of carboxypeptidase E deficiency on progastrin processing and gastrin messenger ribonucleic acid expression in mice with the fat mutation. In: Endocrinology. 1997 ; Vol. 138, No. 5. pp. 1959-1963.
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