scholarly journals Nateglinide Stimulates Glucagon-Like Peptide-1 Release by Human Intestinal L Cells via a KATP Channel-Independent Mechanism

2011 ◽  
Vol 34 (5) ◽  
pp. 671-676 ◽  
Author(s):  
Yoshiro Kitahara ◽  
Kyoko Miura ◽  
Reiko Yasuda ◽  
Haruka Kawanabe ◽  
Shimpei Ogawa ◽  
...  
2019 ◽  
Vol 316 (5) ◽  
pp. G574-G584 ◽  
Author(s):  
Charlotte Bayer Christiansen ◽  
Samuel Addison Jack Trammell ◽  
Nicolai Jacob Wewer Albrechtsen ◽  
Kristina Schoonjans ◽  
Reidar Albrechtsen ◽  
...  

A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3.5- and 2.9-fold, respectively. Furthermore, we find that responses depend on BA absorption followed by basolateral activation of the BA-receptor Takeda-G protein-coupled-receptor 5. Surprisingly, the apical sodium-dependent BA transporter, which serves to absorb conjugated BAs, was not required for colonic conjugated BA absorption or conjugated BA-induced peptide secretion. In conclusion, we demonstrate that BAs represent a major physiological stimulus for colonic L-cell secretion.NEW & NOTEWORTHY By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acids in the colon and thus add to the existing literature described for L cells in the ileum.


2010 ◽  
Vol 138 (5) ◽  
pp. S-403-S-404 ◽  
Author(s):  
Alexander D. Kazberouk ◽  
Francesco Giovinazzo ◽  
Andrew Timberlake ◽  
Betty De Smet ◽  
Roswitha Pfragner ◽  
...  

2009 ◽  
Vol 297 (4) ◽  
pp. G663-G671 ◽  
Author(s):  
Tohru Hira ◽  
Taisuke Mochida ◽  
Kyoko Miyashita ◽  
Hiroshi Hara

Glucagon-like peptide-1 (GLP-1) is released from enteroendocrine cells (L cells) in response to food ingestion. The mechanism by which dietary peptides stimulate GLP-1 secretion in the gut is unknown. In the present study, we found that a hydrolysate prepared from zein, a major corn protein [zein hydrolysate (ZeinH)], strongly stimulates GLP-1 secretion in enteroendocrine GLUTag cells. Stimulatory mechanisms of GLP-1 secretion induced by ZeinH were investigated in the rat small intestine under anesthesia. Blood was collected through a portal catheter before and after ZeinH administration into different sites of the small intestine. The duodenal, jejunal, and ileal administration of ZeinH induced dose-dependent increases in portal GLP-1 concentration. GLP-1 secretion in response to the ileal administration of ZeinH was higher than that in the duodenal or jejunal administration. Capsaicin treatment on esophageal vagal trunks abolished the GLP-1 secretion induced by duodenal ZeinH but did not affect the secretion induced by jejunal or ileal ZeinH. These results suggest that ZeinH in the jejunum or ileum directly stimulates GLP-1 secretion but duodenal ZeinH indirectly stimulates GLP-1 secretion via the vagal afferent nerve. A direct blood sampling method from the duodenal vein and ileal mesenteric vein revealed that ZeinH administered into the ligated duodenal loop enhanced GLP-1 concentration in the ileal mesenteric vein but not in the duodenal vein. This confirmed that ZeinH in the duodenum induces GLP-1 secretion from L cells located in the ileum by an indirect mechanism. These results indicate that a potent GLP-1-releasing peptide, ZeinH, induces GLP-1 secretion by direct and indirect mechanisms in the rat intestine.


2017 ◽  
Vol 292 (26) ◽  
pp. 10855-10864 ◽  
Author(s):  
Kazuki Harada ◽  
Tetsuya Kitaguchi ◽  
Taichi Kamiya ◽  
Kyaw Htet Aung ◽  
Kazuaki Nakamura ◽  
...  

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1089-1098 ◽  
Author(s):  
Roman Iakoubov ◽  
Angelo Izzo ◽  
Andrea Yeung ◽  
Catharine I. Whiteside ◽  
Patricia L. Brubaker

Long-chain, monounsaturated fatty acids (FAs) stimulate secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1) from the intestinal L cell. Because the atypical protein kinase C (PKC), PKCζ, is involved in FA signaling in many cells, the role of PKCζ in FA-induced GLP-1 secretion was investigated, using the murine GLUTag L cell line and primary rat intestinal L cells. GLUTag cells expressed mRNA for several PKC isoforms, including PKCζ, and PKCζ protein was localized throughout the cytoplasm in GLUTag and primary L cells as well as normal mouse and rat L cells. Treatment with oleic acid (150–1000 μm) for 2 h increased GLP-1 secretion (P < 0.001), and this was abrogated by the PKCζ inhibitor ZI (P < 0.05) and PKCζ small interfering RNA transfection (P < 0.05) but not inhibition of classical/novel PKC isoforms. Although most PKCζ was localized in the particulate compartment of GLUTag cells, oleate treatment did not alter PKCζ levels or activity in this cell fraction. GLUTag cells expressed mRNA for the Gq-coupled FA receptor GPR120; however, oleic acid did not induce any changes in Akt, MAPK, or calcium, and pretreatment with LY294002 and PD98059 to inhibit phosphatidylinositol 3-kinase and MAPK, respectively, did not prevent the effects of oleic acid. Finally, GLUTag cells also released GLP-1 in response to arachidonic acid (P < 0.001) but were not affected by other long-chain FAs. These findings demonstrate that PKCζ is required for oleic acid-induced GLP-1 secretion. This enzyme may therefore serve as a therapeutic target to enhance GLP-1 release in type 2 diabetes.


2011 ◽  
Vol 589 (5) ◽  
pp. 1081-1093 ◽  
Author(s):  
G. J. Rogers ◽  
G. Tolhurst ◽  
A. Ramzan ◽  
A. M. Habib ◽  
H. E. Parker ◽  
...  

2003 ◽  
Vol 81 (11) ◽  
pp. 1005-1012 ◽  
Author(s):  
Patricia L Brubaker ◽  
Younes Anini

The proglucagon-derived peptide family consists of three highly related peptides, glucagon and the glucagon-like peptides GLP-1 and GLP-2. Although the biological activity of glucagon as a counter-regulatory hormone has been known for almost a century, studies conducted over the past decade have now also elucidated important roles for GLP-1 as an antidiabetic hormone, and for GLP-2 as a stimulator of intestinal growth. In contrast to pancreatic glucagon, the GLPs are synthesized in the intestinal epithelial L cells, where they are subject to the influences of luminal nutrients, as well as to a variety of neuroendocrine inputs. In this review, we will focus on the complex integrative mechanisms that regulate the secretion of these peptides from L cells, including both direct and indirect regulation by ingested nutrients.Key words: GLP-1, GLP-2, intestine, secretion, nutrients, neural.


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