scholarly journals Physiological Gut Oxygenation Alters GLP-1 Secretion from the Enteroendocrine Cell Line STC-1

2018 ◽  
Vol 62 (3) ◽  
pp. 1700568 ◽  
Author(s):  
Alina Kondrashina ◽  
Dmitri Papkovsky ◽  
Linda Giblin
2006 ◽  
Vol 191 (1) ◽  
pp. 159-170 ◽  
Author(s):  
Raylene A Reimer

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.


2011 ◽  
Vol 37 (2) ◽  
pp. 167-177 ◽  
Author(s):  
M. Kurogi ◽  
M. Miyashita ◽  
Y. Emoto ◽  
Y. Kubo ◽  
O. Saitoh

Diabetologia ◽  
2007 ◽  
Vol 50 (10) ◽  
pp. 2181-2189 ◽  
Author(s):  
A. K. Simpson ◽  
P. S. Ward ◽  
K. Y. Wong ◽  
G. J. Collord ◽  
A. M. Habib ◽  
...  

1998 ◽  
Vol 50 (3) ◽  
pp. 183-189 ◽  
Author(s):  
Fei Ye ◽  
Anne-Marie Chevrier ◽  
Dominique Langlois ◽  
Jean-Claude Cuber ◽  
Jose M. Saez ◽  
...  

2012 ◽  
Vol 302 (1) ◽  
pp. C210-C219 ◽  
Author(s):  
Bhavik P. Shah ◽  
Pin Liu ◽  
Tian Yu ◽  
Dane R. Hansen ◽  
Timothy A. Gilbertson

Fatty acid-induced stimulation of enteroendocrine cells leads to release of the hormones such as cholecystokinin (CCK) that contribute to satiety. Recently, the fatty acid activated G protein-coupled receptor GPR120 has been shown to mediate long-chain unsaturated free fatty acid-induced CCK release from the enteroendocrine cell line, STC-1, yet the downstream signaling pathway remains unclear. Here we show that linoleic acid (LA) elicits membrane depolarization and an intracellular calcium rise in STC-1 cells and that these responses are significantly reduced when activity of G proteins or phospholipase C is blocked. LA leads to activation of monovalent cation-specific transient receptor potential channel type M5 (TRPM5) in STC-1 cells. LA-induced TRPM5 currents are significantly reduced when expression of TRPM5 or GPR120 is reduced using RNA interference. Furthermore, the LA-induced rise in intracellular calcium and CCK secretion is greatly diminished when expression of TRPM5 channels is reduced using RNA interference, consistent with a role of TRPM5 in LA-induced CCK secretion in STC-1 cells.


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