PEPTONES STIMULATE BOTH THE SECRETION OF THE INCRETIN HORMONE GLUCAGON-LIKE PEPTIDE-1 AND THE TRANSCRIPTION OF THE PROGLUCAGON GENE

Truncated glucagon-like peptide (GLP)-1 is a potent incretin. Its synt hesis and secretion are modulated by food, but the influence of indivi dual nutrients remains to be established. The hypothesis that protein hydrolysates (peptones) can directly regulate both GLP-1 secretion and proglucagon (PG) gene transcription mas tested in this study, ex vivo in the isolated vascularly perfused rat intestine and in vitro in the murine enteroendocrine cell line STC-1. Peptones mere albumin egg hyd rolysate (AEH) and meat hydrolysate (MH). We demonstrate in these two models that peptones dose-dependently stimulate GLP-1 release, whereas isocaloric quantities of bovine serum albumin or of an amino acid mix ture had no stimulatory effect. A strong and rapid increase of PG RNA level was observed in STC-1 cells treated with peptones (14-fold and 7 -fold increase after 4 h of incubation with 3% wt/vol MH and AEH, resp ectively). Peptones also increased the PG RNA level in the colonic PG- expressing cell line GLUTag. In contrast, peptones did not modify the PG RNA level in two pancreatic glucagon-producing cell lines, namely, the RINm5F and INR1G9 cells. The peptone effect in STC-1 cells mas com pletely abolished by blocking transcription before MH treatment. The s tability of proglugacon transcripts was not modified by MH treatment, but nascent transcripts were more abundant in STC-1 cells preincubated with MH. Finally, MH treatment strongly stimulated (15-fold stimulati on) the transcriptional activity of two PG gene promoter fragments (-1 100 abd -350 base pair) linked to the CAT reporter gene transiently tr ansfected in STC-1 cells. Overall, peptones evoke an as yet undescribe d release of GLP-1 when brought into contact with native intestinal L- cells or with STC-1 enteroendocrine cells. The increased transcription of the glucagon gene in the latter system suggests an important role of protein hydrolysates in the control of not only the secretion but a lso the synthesis of the incretin hormone.