Abstract
Secretion of the intestinal proglucagon-derived peptides (PGDPs) including the incretin glucagon-like peptide-1 (GLP-1) is regulated, at least in part, by the duodenal hormone glucose-dependent insulinotropic peptide (GIP) through a protein kinase (PK) A-dependent pathway. It has been demonstrated that the activation of PKA increases the synthesis of some intestinal PGDPs, particularly the glucagon-like immunoreactive (GLI) peptides glicentin and oxyntomodulin. However, the effects of GIP on GLI and GLP-1 synthesis are not known. Fetal rat intestinal cells in culture were therefore treated for up to 24 h with 5mm dbcAMP or 10−6 m GIP and the changes in glicentin, oxyntomodulin, GLP-1x-37 and GLP-1x-36NH2 secretion and synthesis were examined by RIA and HPLC. Both dbcAMP and GIP increased the acute (2 h; to 224±21 and 256±20% of controls, respectively,P<0.001) and chronic (24 h; to 230±22 and 130±6% of controls, respectively,P<0.001) secretion of intestinal PGDPs. In contrast, the total culture content of PGDPs was increased only after 24 h of incubation (to 156±15 and 125±7% of controls for dbcAMP and GIP, respectively,P<0.01). HPLC analysis confirmed that the intestinal cultures produced the GLI peptides glicentin and oxyntomodulin, as well as the biologically active forms of GLP-1, GLP-77–37 and GLP-17-36NH2. The relative proportion of these peptides was not altered by treatment with dbcAMP or GIP. Thus, in addition to its effects on GLP-1 release from the rat intestine, GIP appears to be an important regulator of the synthesis of this insulinotropic peptide.
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Jackson Huang, T.H., Brubaker, P.L. Synthesis and secretion of glucagon-like peptide-1 by fetal rat intestinal cells in culture. Endocr 3, 499–503 (1995). https://doi.org/10.1007/BF02738824
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DOI: https://doi.org/10.1007/BF02738824