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Meat hydrolysate and essential amino acid-induced glucagon-like peptide-1 secretion, in the human NCI-H716 enteroendocrine cell line, is regulated by extracellular signal-regulated kinase1/2 and p38 mitogen-activated protein kinases.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Reimer, Raylene A. |
| Copyright Year | 2006 |
| Abstract | Glucagon-like peptide-1 (GLP-1) is a potent insulin secretagogue released from L-cells in the intestine. Meat hydrolysate (MH) is a powerful activator of GLP-1 secretion in the human enteroendocrine NCI-H716 cell line, but the mechanisms involved in nutrient-stimulated GLP-1 secretion are poorly understood. The objective of this study was to characterize the intracellular signalling pathways regulating MH- and amino acid-induced GLP-1 secretion. Individually, the pharmacological inhibitors, SB203580 (inhibitor of p38 mitogen-activated protein kinase (MAPK)), wortmannin (inhibitor of phosphatidyl inositol 3-kinase) and U0126 (inhibitor of mitogen activated or extracellular signal-regulated protein kinase (MEK1/2) upstream of extracellular signal-regulated kinase (ERK)1/2) all inhibited MH-induced GLP-1 secretion. Further examination of the MAPK pathway showed that MH increased the phosphorylation of ERK1/2, but not p38 or c-Jun N-terminal kinase over 2-15 min. Incubation with SB203580 resulted in a decrease in phosphorylated p38 MAPK and a concomitant increase in the phosphorylation of ERK1/2. Phosphorylation of ERK1/2 was augmented by co-incubation of MH with SB203580. Inhibitors of protein kinase A and protein kinase C did not inhibit MH-induced GLP-1 secretion. In contrast to non-essential amino acids, essential amino acids (EAAs) increased GLP-1 secretion and similar to MH, activated ERK1/2. However, they also activated p38-suggesting type of protein may affect GLP-1 secretion. In conclusion, there appears to be a crosstalk between p38 and ERK1/2 MAPK in the human enteroendocrine cell with the activation of ERK1/2 common to both MH and EAA. Understanding the cellular pathways involved in nutrient-stimulated GLP-1 secretion has important implications for the design of new treatments aimed at increasing endogenous GLP-1 release in type-2 diabetes and obesity. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://joe.bioscientifica.com/downloadpdf/journals/joe/191/1/1910159.pdf |
| PubMed reference number | 17065399v1 |
| Volume Number | 191 |
| Issue Number | 1 |
| Journal | The Journal of endocrinology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Amino Acids, Essential Cross Reactions Enteroendocrine Cell Excitatory Amino Acids Glucagon-Like Peptide 1 Glucagon-Like Peptide Receptors Inositol Intestinal Wall Tissue Mitogen-Activated Protein Kinases Mitogens Obesity Pharmacology Phosphatidylinositols SB 203580 U 0126 biological signaling eIF-2 Kinase glucagon (rDNA) mitogen-activated protein kinase p38 wortmannin |
| Content Type | Text |
| Resource Type | Article |
