GLUTag cells generated by the Drucker lab are a stable immortalized relatively differentiated murine enteroendocrine cell line that express the proglucagon gene and secretes the glucagon-like peptides in a regulated manner

This cell line was isolated from a glucagon-producing enteroendocrine cell tumor that arose in glucagon gene-SV40 T antigen transgenic mice Glucagon gene 5'-flanking sequences direct expression of simian virus 40 large T antigen to the intestine, producing carcinoma of the large bowel in transgenic mice. J Biol Chem. 1992 May 25;267 (15): 10705-8

GLUTag cells were serially passaged in nude mice, and gave rise to glucagonomas that exhibit a stable phenotype of glucagon gene expression over a 4-8 week period as shown in Inhibition of pancreatic glucagon gene expression in mice bearing a subcutaneous glucagon-producing GLUTag transplantable tumor. Mol Endocrinol. 1992 Dec;6(12):2175-84.

In contrast to mouse STC-1 cells, GLUTag cells appear quite well differentiated, and recapitulate the responsiveness of primary non-transformed rat intestinal cell cultures to physiological and pharmacological secretagogues as demonstrated in Activation of proglucagon gene transcription by protein kinase-A in a novel mouse enteroendocrine cell line. Mol Endocrinol. 1994 Dec;8(12):1646-55 and Regulation of glucagon-like peptide-1 synthesis and secretion in the GLUTag enteroendocrine cell line. Endocrinology. 1998 Oct;139(10):4108-14.

Gribble and colleagues used a transgenic approach to isolate non-transformed L cells using a fluorescent protein expressed in L cells under the control of the proglucagon promoter. Isolated sorted GLP-1-secreting L cells were analyzed in primary culture. These cells were directly glucose-responsive, and secreted GLP-1 in response to agents causing membrane depolarization or neurotransmitter-stimulated signal transduction. Moreover, comparison of key genes and proteins expressed in and signal transduction pathways operative in L cells with the same genes, proteins, and pathways utilized by the GLUTag cell line revealed remarkable similarities between non-immortalized murine L cells and GLUTag cells. Remarkably, primary mouse L cell cultures and GLUTag cells exhibit a similar Ec50 for glucose stimulation of GLP-1 secretion, comparable responsivity to forskolin/IBMX and bombesin and very similar patterns of gene expression profiles for key receptors, glucose sensorss, ion channels, and regulatory molecules (Figure 4 and Table S1); See Glucose sensing in L cells: a primary cell study Cell Metab. 2008 Dec;8(6):532-9

GLUTag cells have been utilized extensively for the analysis of GLP-1/GLP-2 secretagogues, and for studies of enteroendocrine glucagon gene transcription. 

GLUTag cells have also been studied for analysis of CCK biosynthesis and secretion. A susbet of microarray data from studies of FXR E-MTAB-2199 - GW4064 treatment on GLUTag cells is found here https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-2199/

GLUTag cells have been propagated intermittently since 1991 in the Drucker lab, and early passage cells have retained their differentiated phenotype both in vitro and in vivo. Indeed, independent studies carried out over a decade later reveal preserved glucose competence, with GLP-1 secretion stimulated over a range of glucose concentrations, likely via closure of KATP channels, as shown in Glucose-sensing in glucagon-like Peptide-1-secreting cells. Diabetes. 2002 Sep;51(9):2757-63.

Furthermore, GLUTag cells control GLP-1 secretion in part through depolarization events triggered not only by metabolizable sugars (glucose or fructose) but also by through non-metabolizable sugars through a SGLT-dependent mechanism, as outlined in A Novel Glucose-Sensing Mechanism Contributing to Glucagon-Like Peptide-1 Secretion From the GLUTag Cell Line. Diabetes. 2003 May;52(5):1147-54

Moreover, glutamine has also been shown to be a potent secretagogue in GLP-1 release as outlined in Glutamine potently stimulates glucagon-like peptide-1 secretion from GLUTag cells. Diabetologia 2004 Sep;47(9):1592-601. Epub 2004 Sep

Similarly, Reimann, Gribble and colleagues have characterized ion channel current and channel expression in GLUTag cells.  These studies demonstrated that GLP-1 release in GLUTag cells is not dependent on the firing of Na(+)-carrying action potentials but requires membrane depolarisation and Ca(2+) entry through L-type Ca(2+) channels. See Characterisation and functional role of voltage gated cation conductances in the Glucagon-like peptide-1 secreting GLUTag cell line. J Physiol. 2004 Dec 20; [Epub ahead of print]

Analysis of GLP-1 secretion in GLUTag cells indicates that peptides or pharmacological agents that increase cyclic AMP also increase levels of intracellular calcium, events coupled to stimulation of GLP-1 secretion in GLUTag cells.  Enhanced levels of cyclic AMP appear to sensitize the L cells to nutrient-related secretagogues such as glucose See Cyclic AMP triggers glucagon-like peptide-1 secretion from the GLUTag enteroendocrine cell line. Diabetologia. 2007 Jul 21; [Epub ahead of print]

Friedlander and colleagues studied the importance of cAMP, adenylate cyclase, and phsophodiesterase (PDE) using primary murine colonic L cells and GLUTagcells. L cells expressed high levels of adenylate cyclase isoforms 2, 5, 6, 8, and 9. AC2 was preferentially expressed in L cells. Multiple PDE  isoforms were also expressed in L cells. Activation of cyclic GMP also stimulated GLP-1 secretion, with PDE3 likely important for these effects. See Role of phosphodiesterase and adenylate cyclase isozymes in murine colonic glucagon like peptide 1 secreting cells Br J Pharmacol. 2010 Nov 3. doi: 10.1111/j.1476-5381.2010.01107.

To review some of the GLUTag cell literature, See:

Inhibition of pancreatic glucagon gene expression in mice bearing a subcutaneous glucagon-producing GLUTag transplantable tumor. Mol Endocrinol. 1992 Dec;6(12):2175-84.

Molecular pathophysiology of glucagon-SV40 T antigen transgenic mice. Am J Physiol. 1994 Nov;267(5 Pt 1):E629-35. Review.

Activation of proglucagon gene transcription by protein kinase-A in a novel mouse enteroendocrine cell line. Mol Endocrinol. 1994 Dec;8(12):1646-55

The proglucagon gene upstream enhancer contains positive and negative domains important for tissue-specific proglucagon gene transcription. Mol Endocrinol. 1995 Oct;9(10):1306-20.

The caudal homeobox protein cdx-2/3 activates endogenous proglucagon gene expression in InR1-G9 islet cells. Mol Endocrinol. 1997 Feb;11(2):203-9.

Peptones stimulate cholecystokinin secretion and gene transcription in the intestinal cell line STC-1. Endocrinology. 1997 Mar;138(3):1137-44.

Expression of SNARE proteins in enteroendocrine cell lines and functional role of tetanus toxin-sensitive proteins in cholecystokinin release. FEBS Lett. 1998 Mar 20;425(1):66-70.

Peptones stimulate both the secretion of the incretin hormone glucagon-like peptide 1 and the transcription of the proglucagon gene. Diabetes. 1998 Jul;47(7):1038-45

Regulation of glucagon-like peptide-1 synthesis and secretion in the GLUTag enteroendocrine cell line. Endocrinology. 1998 Oct;139(10):4108-14

Divergent regulation of human and rat proglucagon gene promoters in vivo. Am J Physiol. 1999 Oct;277(4 Pt 1):G829-37

Fatty acid-induced cholecystokinin secretion and changes in intracellular Ca2+ in two enteroendocrine cell lines, STC-1 and GLUTag. J Physiol. 2000 Oct 1;528 Pt 1:165-76

Coregulation of glucagon-like peptide-1 synthesis with proglucagon and prohormone convertase 1 gene expression in enteroendocrine GLUTag cells. Endocrinology. 2001 Jan;142(1):37-42.

Rab3a controls exocytosis in cholecystokinin-secreting cells. FEBS Lett. 2001 Aug 10;503(1):19-24

Foxa3 (HNF-3gamma) binds to and activates the rat proglucagon gene promoter but is not essential for proglucagon gene expression. Biochem J. 2002 Sep 1;366(Pt 2):633-41.

Glucose-sensing in glucagon-like peptide-1-secreting cells. Diabetes. 2002 Sep;51(9):2757-63

Pax-2 activates the proglucagon gene promoter but is not essential for proglucagon gene expression or development of proglucagon-producing cell lineages in the murine pancreas or intestine. Mol Endocrinol. 2002 Oct;16(10):2349-59

Transcriptional activation of the proglucagon gene by lithium and beta-catenin in intestinal endocrine L cells. J Biol Chem. 2003 Jan 10;278(2):1380-7.

Role of leptin in the regulation of glucagon-like peptide-1 secretion. Diabetes. 2003 Feb;52(2):252-9

A Novel Glucose-Sensing Mechanism Contributing to Glucagon-Like Peptide-1 Secretion From the GLUTag Cell Line. Diabetes. 2003 May;52(5):1147-54

Differentiation phenotypes of pancreatic islet beta- and alpha-cells are closely related with homeotic genes and a group of differentially expressed genes. Gene. 2004 Apr 28;331:53-63

TCF-4 mediates cell-type specific regulation of proglucagon gene expression by beta-catenin and GSK-3beta. J Biol Chem. 2004 Nov 2; [Epub ahead of print]

Glutamine potently stimulates glucagon-like peptide-1 secretion from GLUTag cells. Diabetologia. 2004 Sep;47(9): 1592-601. Epub 2004 Sep

Pdx-1 is not sufficient for repression of proglucagon gene transcription in islet or enteroendocrine cells. Endocrinology. 2005 Jan;146(1):441-9. Epub 2004 Oct 07

TCF-4 mediates cell type-specific regulation of proglucagon gene expression by beta-catenin and glycogen synthase kinase-3beta. J Biol Chem. 2005 Jan 14;280(2):1457-64

Characterization and functional role of voltage gated cation conductances in the glucagon-like peptide-1 secreting GLUTag cell line. J Physiol. 2005 Feb 15;563(Pt 1):161-75

PKA independent and cell type specific activation of the expression of caudal homeobox gene Cdx-2 by cyclic AMP. FEBS J. 2005 Jun;272(11):2746-59

The neurotransmitters glycine and GABA stimulate glucagon-like peptide-1 release from the GLUTag cell line. J Physiol. 2005 Dec 15;569(Pt 3):761-72.

Vesicular storage and secretion of l-glutamate from glucagon-like peptide 1-secreting clonal intestinal L cells. J Neurochem. 2006 Jan;96(2):550-60.

Protein kinase Czeta is required for oleic acid-induced secretion of glucagon-like peptide-1 by intestinal endocrine L cells. Endocrinology. 2007 Mar;148(3):1089-98. Epub 2006 Nov 16.

Cyclic AMP triggers glucagon-like peptide-1 secretion from the GLUTag enteroendocrine cell line. Diabetologia. 2007 Jul 21; [Epub ahead of print]

T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15075-80. Epub 2007 Aug 27

A Role for Intestinal Endocrine Cell-Expressed GPR119 in Glycemic Control by Enhancing GLP-1 and GIP Release Endocrinology. 2008 Jan 17; 2008 May;149(5):2038-47.

Cross Talk between the Insulin and Wnt Signaling Pathways: Evidence from Intestinal Endocrine L Cells Endocrinology. 2008 May;149(5):2341-51.

Insulin-secreting L-cells for the treatment of insulin-dependent diabetes  Biochem Biophys Res Commun. 2008 Jun 20;371(1):39-43

Insulin regulates glucagon-like peptide-1 secretion from the enteroendocrine L cell. Endocrinology. 2009 Feb;150(2):580-91. Epub 2008 Sep 25

Epac is involved in cAMP-stimulated proglucagon expression and hormone production, but not hormone secretion in pancreatic alpha and intestinal L cell lines. Am J Physiol Endocrinol Metab. 2009 Jan;296(1):E174-81. Epub 2008 Oct 14

Glucose sensing in L cells: a primary cell study Cell Metab. 2008 Dec;8(6):532-9

GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell Diabetes. 2009 May;58(5):1058-66. Epub 2009 Feb 10.

Development and characterization of a tissue engineered pancreatic substitute based on recombinant intestinal endocrine L-cells Biotechnol Bioeng. 2009 Jul 1;103(4):828-34.

A selective small molecule GLP-1 secretagogue acting via depolarization and Ca2+ influx J Endocrinol. 2009 Jun;201(3):361-7. Epub 2009 Mar 30

 

The role of the PDE4D cAMP phosphodiesterase in the regulation of glucagon-like peptide-1 release Br J Pharmacol. 2009 Jun;157(4):633-44. Epub 2009 Apr 9.

GLP-1 secretion is enhanced directly in the ileum, but indirectly in the duodenum by a newly identified potent stimulator, zein hydrolysate in rats Am J Physiol Gastrointest Liver Physiol. 2009 Aug 6. [Epub ahead of print]

Role of MGAT2 and DGAT1 in the release of gut peptides after triglyceride ingestion. Biochem Biophys Res Commun. 2009 Sep 1. [Epub ahead of print]

The Rho Guanosine 5'-Triphosphatase, Cell Division Cycle 42, Is Required for Insulin-Induced Actin Remodeling and Glucagon-Like Peptide-1 Secretion in the Intestinal Endocrine L Cell. Endocrinology. 2009 Oct 9. [Epub ahead of print]

A Cell-Based Approach for Diabetes Treatment Using Engineered Non-beta Cells. J Diabetes Sci Technol. 2009 May 1;3(3):555-561.

REEP2 Enhances Sweet Receptor Function by Recruitment to Lipid Rafts. J Neurosci. 2010 Oct 13;30(41):13774-83.

Role of phosphodiesterase and adenylate cyclase isozymes in murine colonic glucagon like peptide 1 secreting cells Br J Pharmacol. 2010 Nov 3. doi: 10.1111/j.1476-5381.2010.01107.

Glutamine Triggers and Potentiates Glucagon-Like Peptide-1 Secretion by Raising Cytosolic Ca2+ and cAMP Endocrinology. 2011 Jan 5. [Epub ahead of print]

Electrical activity-triggered Glucagon-Like Peptide-1 secretion from primary murine L-cells J Physiol. 2011 Jan 4.

Targeting the PI3K/mTOR Pathway in Murine Endocrine Cell Lines In Vitro and in Vivo Effects on Tumor Cell Growth Am J Pathol. 2011 Jan;178(1):336-44. Epub 2010 Dec 23

PPARβ/δ Activation Induces Enteroendocrine L Cell GLP-1 Production Gastroenterology. 2011 Feb 4

Synaptotagmin-7 as a positive regulator of glucose-induced glucagon-like peptide-1 secretion in mice Diabetologia. 2011 Mar 22. [Epub ahead of print]

GLP-1 Secretion in Response to Oral and Luminal Palatinose (Isomaltulose) in Rats J Nutr Sci Vitaminol (Tokyo). 2011;57(1):30-5

Nkx6.2 synergizes with Cdx-2 in stimulating proglucagon gene expression World J Diabetes. 2011 May 15;2(5):66-74.

Molecular mechanisms underlying bile acid stimulated glucagon-like peptide-1 secretion. Br J Pharmacol. 2011 Jun 30. doi: 10.1111/j.1476-5381.2011.01561.x. [Epub ahead of print

Exendin-4 upregulates the expression of Wnt-4, a novel regulator of pancreatic β-cell proliferation Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E864-72

Mechanisms Underlying Metformin-Induced Secretion of Glucagon-Like Peptide-1 from the Intestinal L Cell Endocrinology 2011 Dec;152(12):4610-9

GPR119 agonists mediate GLP-1 secretion from mouse enteroendocrine cells through glucose-independent pathways

Br J Pharmacol. 2012 Apr;165(8):2799-807

Interleukin-6 enhances insulin secretion by increasing L cell and a cell glucagon-like peptide-1 secretion Nature Medicine 2011 Oct 30;17(11):1481-9

Combinatorial insulin secretion dynamics of recombinant hepatic and enteroendocrine cells. Biotechnol Bioeng 2012 Apr;109(4):1074-82.

Novel Biological Action of the Dipeptidylpeptidase-IV Inhibitor, Sitagliptin, as a Glucagon-Like Peptide-1 Secretagogue Endocrinology. 2012 Feb;153(2):564-73

Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein–Coupled Receptor FFAR2 Diabetes 2012 Feb;61(2):364-71

Predominant role of active versus facilitative glucose transport for glucagon-like peptide-1 secretion Diabetologia. 2012 Sep;55(9):2445-55

Insulin detemir enhances proglucagon gene expression in the intestinal L cells via stimulating β-catenin and CREB activities Am J Physiol Endocrinol Metab. 2012 Sep;303(6):E740-51

Metformin protects against lipoapoptosis and enhances GLP-1 secretion from GLP-1-producing cells J Gastroenterol. 2012 Aug 2.

Role of fatty acid transport protein 4 in oleic acid-induced glucagon-like peptide-1 secretion from murine intestinal L cells Am J Physiol Endocrinol Metab. 2012 Oct;303(7):E899-907

Somatostatin receptor 5 and cannabinoid receptor 1 activation inhibit secretion of glucose-dependent insulinotropic polypeptide from intestinal K cells in rodents Diabetologia. 2012 Nov;55(11):3094-103

Activation of Enteroendocrine Membrane Progesterone Receptors Promotes Incretin Secretion and Improves Glucose Tolerance in Mice Diabetes. 2012 Aug 29

Molecular mechanisms of lipoapoptosis and metformin protection in GLP-1 secreting cells Biochem Biophys Res Commun. 2012 Oct 12;427(1):91-5

A Potent Class of GPR40 Full Agonists Engages the EnteroInsular Axis to Promote Glucose Control in RodentsPLoS One. 2012;7(10):e46300. doi: 10.1371/journal.pone.0046300

Regulation of GPR119 receptor activity with endocannabinoid - like lipids Am J Physiol Endocrinol Metab. 2012 Oct 16

Activation of Prostaglandin E Receptor 4 Triggers Secretion of Gut Hormone Peptides GLP-1, GLP-2, and PYY Endocrinology. 2012 Nov 9. [Epub ahead of print]

The GPRC6A receptor is involved in amino acid-induced glucagon-like peptide-1 secretion from GLUTag cells J Biol Chem. 2012 Dec 26

Frog skin peptides (tigerinin-1R, magainin-AM1,-AM2, CPF-AM1, and PGla-AM1) stimulate secretion of glucagon-like peptide 1 (GLP-1) by GLUTag cell Biochem Biophys Res Commun. 2013 Jan 3. doi:pii: S0006-291X(12)02476-X

Antitumor Effect of Everolimus in Preclinical Models of High Grade Gastroenteropancreatic Neuroendocrine Carcinoma Neuroendocrinology. 2013 Jan 23

Activation of FFA1 mediates GLP-1 secretion in mice. Evidence for allosterism at FFA1 Mol Cell Endocrinol. 2013 Feb 9. doi:pii: S0303-7207(13)00032-4

The Sorting of Proglucagon to Secretory Granules is Mediated by CPE and Intrinsic Sorting Signals J Endocrinol. 2013 Feb 15

Curcumin stimulates glucagon-like peptide-1 secretion in GLUTag cells via Ca2+/calmodulin-dependent kinase II activation Biochem Biophys Res Commun. 2013 May 6. doi:pii: S0006-291X(13)00746-

High-Throughput Screening for GPR119 Modulators Identifies a Novel Compound with Anti-Diabetic Efficacy in db/db Mice PLoS One. 2013 May 21;8(5):e63861.

Stimulation of proglucagon gene expression by human GPR119 in enteroendocrine L-cell line GLUTag Mol Endocrinol. 2013 Aug;27(8):1267-82.

The Pharmacology of a Potent and Selective Agonist, TUG-891, Demonstrates Both Potential Opportunity and Possible Challenges to Therapeutic Agonism of FFA4 (GPR120) Mol Pharmacol. 2013 Aug 26

Evidence for paracrine/autocrine regulation of GLP-1-producing cells Am J Physiol Cell Physiol. 2013 Nov 15;305(10):C1041-9.

Oligopeptides stimulate glucagon-like peptide-1 secretion in mice through proton-coupled uptake and the calcium-sensing receptor Diabetologia. 2013 Dec;56(12):2688-96

Role of vesicle-associated membrane protein 2 in exocytosis of glucagon-like peptide-1 from the murine intestinal L cell Diabetologia. 2014 Apr;57(4):809-18

Gastrointestinal hormonal responses upon GPR119 activation in lean and diseased rodent models of type 2 diabetes Int J Obes (Lond). 2014 2014 Oct;38(10):1365-73

GLP-1 Amidation Efficiency Along the Length of the Intestine in Mice, Rats and Pigs and in GLP-1 Secreting Cell Lines Peptides. 2014 May;55:52-7.

Fructose stimulates GLP-1 but not GIP secretion in mice, rats and humans Am J Physiol Gastrointest Liver Physiol. 2014 Apr 1;306(7):G622-30

Glucagon-Like Peptide-1 Secreting Cell Function as well as Production of Inflammatory Reactive Oxygen Species Is Differently Regulated by Glycated Serum and High Levels of Glucose Mediators Inflamm. 2014; 923120

Glucagon-like peptide-1 production in the GLUTag cell line is impaired by free fatty acids via endoplasmic reticulum stress Metabolism. 2014 Feb 25. pii: S0026-0495(14)00051-1

A nondigestible saccharide, fructooligosaccharide, increases the promotive effect of a flavonoid, α-glucosyl-isoquercitrin, on glucagon-like peptide 1 (GLP-1) secretion in rat intestine and enteroendocrine cells Mol Nutr Food Res.  2014 Jul;58(7):1581-4

Circadian secretion of the intestinal hormone, glucagon-like peptide-1, by the rodent L-cell Diabetes. 2014 Nov;63(11):3674-85

Glugacon-like peptide-2 (GLP-2): broad receptor expression, limited therapeutic effect on intestinal inflammation and novel role in liver regeneration Am J Physiol Gastrointest Liver Physiol. 2014 Aug 1;307(3):G274-85

Therapeutic Effects of a Non-β Cell Bioartificial Pancreas in Diabetic Mice Transplantation. 2014 Sep 15;98(5):507-13

Immunological identification of vesicular nucleotide transporter in intestinal L cells Biol Pharm Bull. 2014;37(7):1090-5

GLP-1 Secretion Is Increased by Inflammatory Stimuli in an IL-6-Dependent Manner, Leading to Hyperinsulinemia and Blood Glucose Lowering Diabetes. 2014 Oct;63(10):3221-9

Trichostatin A Affects the Secretion Pathways of Beta and Intestinal Endocrine Cells Exp Cell Res. 2015 Jan 1;330(1):212-21

Stimulation of glucagon-like peptide-1 secretion downstream of the ligand-gated ion channel TRPA1 Diabetes. 2015 Apr;64(4):1202-10

Tumor Necrosis Factor α Decreases Glucagon-Like Peptide-2 Expression by Up-Regulating G-Protein–Coupled Receptor 120 in Crohn Disease American Journal of Pathology 2015 Jan;185(1):185-96

Bacterial Metabolite Indole Modulates Incretin Secretion from Intestinal Enteroendocrine L Cells Cell Rep. 2014 Nov 20;9(4):1202-8.

Ghrelin is a novel regulator of glucagon-like peptide-1 secretion Diabetes  2014, doi: 10.2337/db14-1176

The insulinotropic effect of insulin-like peptide 5 in vitro and in vivo Biochem J. 2015 Mar 15;466(3):467-73

Responses of GLP-1 secreting L-cells to cytotoxicity resemble pancreatic beta but not alpha cells J Mol Endocrinol. 2015 Feb;54(1):91-104

Glucocorticoids decrease the production of glucagon-like peptide-1 at the transcriptional level in intestinal l-cells Mol Cell Endocrinol 2015 May 5;406:60-7

Glucose tolerance is improved in mice invalidated for the nuclear receptor HNF-4 gamma: a critical role for enteroendocrine cell lineage Diabetes. 2015 Mar 31. pii: db140993

Hypoxia Decreases Glucagon-Like Peptide-1 Secretion from the GLUTag Cell Line Biol Pharm Bull. 2015;38(4):514-21

Integrative function of adrenaline receptors for glucagon-like peptide-1 exocytosis in enteroendocrine L cell lineGLUTag Biochem Biophys Res Commun. 2015 Apr 3. pii: S0006-291X(15)00619-1

Glucocorticoids suppress GLP-1 secretion: possible contribution to their diabetogenic effects Clin Sci (Lond). 2015 Apr 8

The Anthocyanin Delphinidin 3-Rutinoside Stimulates Glucagon-Like Peptide-1 Secretion in Murine GLUTag Cell Line via the Ca2+/Calmodulin-Dependent Kinase II Pathway PLoS One. 2015 May 11;10(5):e0126157

Differential molecular and cellular responses of GLP-1 secreting L-cells and pancreatic alpha cells to glucotoxicity and lipotoxicity Exp Cell Res. 2015 May 28. pii: S0014-4827(15)30006-9

Sustained wash-resistant receptor activation responses of GPR119 agonists Eur J Pharmacol. 2015 Jun 19. pii: S0014-2999(15)30095-9. doi: 10.1016/j.ejphar.2015.06.031

Rice protein hydrolysates stimulate GLP-1 secretion, reduce GLP-1 degradation, and lower the glycemic response in rats

Food Funct. 2015 Aug 5;6(8):2525-34

Chronic Exposure to Tumor Necrosis Factor α Impairs Secretion of Glucagon-like Peptide-1 Endocrinology. 2015 Aug 13:en20151361

In vitro and in vivo insulinotropic properties of the multifunctional frog skin peptide hymenochirin-1B: a structure-activity study Amino Acids 2015 Oct 6. [Epub ahead of print]

The axon guidance molecule Semaphorin 3F is a negative regulator of tumor progression and proliferation in ileal neuroendocrine tumors. Oncotarget. 2015 Oct 2. doi: 10.18632/oncotarget.5481

Increased Glucose-induced Secretion of Glucagon-like Peptide-1 in Mice Lacking the Carcino-Embryonic Antigen-related Cell Adhesion Molecule 2 J Biol Chem. 2015 Nov 19. 

Mathematical Modeling of Interacting Glucose-Sensing Mechanisms and Electrical Activity Underlying Glucagon-Like Peptide 1 Secretion PLoS Comput Biol. 2015 Dec 2;11(12):e1004600.

High-fat diet and palmitate alter the rhythmic secretion of glucagon-like peptide-1 by the rodent L-cell Endocrinology. 2015 Dec 8:en20151732

Altered Expression of Uncoupling Protein 2 in GLP-1-producing Cells after Chronic High Glucose Exposure: Implications for the Pathogenesis of Diabetes Mellitus Am J Physiol Cell Physiol. 2016 Jan 6:ajpcell.00148.2015

Murine GPRC6A Mediates Cellular Responses to L-Amino Acids, but Not Osteocalcin Variants PLoS One. 2016 Jan 19;11(1):e0146846

Peptide production and secretion in GLUTag, NCI-H716 and STC-1 cells: a comparison to native L-cells J Mol Endocrinol. 2016 Jan 27. pii: JME-15-0293

Long acting analogue of the calcitonin gene-related peptide induces positive metabolic effects and secretion of the glucagon-like peptide-1 Eur J Pharmacol. 2016 Jan 22. pii: S0014-2999(16)30004-8

Oleic acid stimulates glucagon-like peptide-1 release from enteroendocrine cells by modulating cell respiration and glycolysis Metabolism. 2016 Mar;65(3):8-17

Glucose-dependent Insulinotropic Peptide Stimulates Glucagon-like Peptide 1 Production by Pancreatic Islets via Interleukin-6, Produced by α Cells Gastroenterology. 2016 Mar 10. pii: S0016-5085(16)00304-8.

Co-culture of clonal beta cells with GLP-1 and glucagon-secreting cell line impacts on beta cell insulin secretion, proliferation and susceptibility to cytotoxin Biochimie. 2016 Mar 22. pii: S0300-9084(16)30034-7

Oxyntomodulin Identified as a Marker of Type 2 Diabetes and Gastric Bypass Surgery by Mass-spectrometry Based Profiling of Human Plasma EBioMedicine 2016 doi:10.1016/j.ebiom.2016.03.034

Functionality and antidiabetic utility of β- and L-cell containing pseudoislets Exp Cell Res. 2016 Apr 8. pii: S0014-4827(16)30074-X

GPR119 agonist AS1269574 activates TRPA1 cation channels to stimulate GLP-1 secretion Mol Endocrinol. 2016 Apr 15:me20151306

Ywhaz/14-3-3ζ deletion improves glucose tolerance through a GLP-1-dependent mechanism Endocrinology 2016 May 11:en20161016

Oral 2-oleyl glyceryl ether improves glucose tolerance in mice through the GPR119 receptor Biofactors 2016 Jun 14. doi: 10.1002/biof.1303.

Oxyntomodulin Identified as a Marker of Type 2 Diabetes and Gastric Bypass Surgery by Mass-spectrometry Based Profiling of Human Plasma EBioMedicine. 2016 May; 7: 112–120

Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119 PLoS One. 2016 Jul 8;11(7):e0158796. doi: 10.1371/journal.pone.0158796

Purification, Conformational Analysis, and Properties of a Family of Tigerinin Peptides from Skin Secretions of the Crowned Bullfrog Hoplobatrachus occipitalis J Nat Prod. 2016 Sep 23;79(9):2350-6

Curcumin improves glucose tolerance via stimulation of glucagon-like peptide-1 secretion Mol Nutr Food Res. 2016 Nov 7. doi: 10.1002/mnfr.201600471

Low-molecular fraction of wheat protein hydrolysate stimulates glucagon-like peptide-1 secretion in an enteroendocrine L cell line and improves glucose tolerance in rats Nutr Res. 2017 Jan;37:37-45.

Hyodeoxycholic acid derivatives as liver X receptor α and G-protein-coupled bile acid receptor agonists Scientific Reports 7, Article number: 43290 (2017) doi:10.1038/srep43290

Endocrine system on chip for a diabetes treatment mode Biofabrication. 2017 Feb 21;9(1):015021

Oncotarget. 2017 Mar 28;8(13):20974-20987 mTOR inhibitors activate PERK signaling and favor viability of gastrointestinal neuroendocrine cell lines

Long chain saturated and unsaturated fatty acids exert opposing effects on viability and function of GLP-1-producing cells: Mechanisms of lipotoxicity PLoS One. 2017 May 16;12(5):e0177605. 

Lysophosphatidylinositol-induced activation of the cation channel TRPV2 triggers glucagon-like peptide-1 secretion in enteroendocrine L cells J Biol Chem. 2017 May 22. pii: jbc.M117.788653.

Pancreatic-derived factor impaired glucagon-like Peptide-1 production from GLUTag enterendorine L-cell line and intestines

Mol Cell Endocrinol https://doi.org/10.1016/j.mce.2017.05.021

Ghrelin Is a Regulator of Glucagon-Like Peptide 1 Secretion and Transcription in Mice Front Endocrinol (Lausanne). 2017 Jun 19;8:135. doi: 10.3389/fendo.2017.00135

Delphinidin 3-rutinoside-rich blackcurrant extract ameliorates glucose tolerance by increasing the release of glucagon-like peptide-1 secretion Food Sci Nutr. 2017 Apr 7;5(4):929-933

Optogenetic analysis of depolarization dependent glucagon-like peptide-1 release Endocrinology2017 Oct 1;158(10):3426-3434

Canagliflozin potentiates GLP-1 secretion and lowers the peak of GIP secretion in rats fed a high-fat high-sucrose diet Biochem Biophys Res Commun. 2017 Oct 14;492(2):161-165 .

Farnesoid X receptor induces Takeda G-protein receptor 5 cross-talk to regulate bile acid synthesis and hepatic metabolism J Biol Chem. 2017 Jun 30;292(26):11055-11069

Hydrogen sulfide and sulfate prebiotic stimulates the secretion of GLP-1 and improves glycaemia in male mice Endocrinology, 2017 Oct 1;158(10):3416-3425

Chylomicrons stimulate incretin secretion in mouse and human cells Diabetologoa 2017 10.1007/s00125-017-4420-2

Commensal bacteria make GPCR ligands that mimic human signalling molecules Nature 2017 Sep 7;549(7670):48-53

A role for methanogens and methane in the regulation of GLP-1 Endocrinol Diab Metab. 2018;1:e6. https://doi.org/10.1002/edm2.6

IL-6-type Cytokine Signaling in Adipocytes Induces Intestinal GLP-1 Secretion Diabetes  2018 Jan;67(1):36-4

Epicatechin potentiation of glucose-stimulated insulin secretion in INS-1 cells is not dependent on its antioxidant activity Acta Pharmacologica Sinica 39, 893–902

CREB/CRTC2 controls GLP-1-dependent regulation of glucose homeostasis FASEB J. 2017 Nov 8. pii: fj.201700845R. doi: 10.1096/fj.201700845R

Glutamine-Elicited Secretion of Glucagon-Like Peptide 1 (GLP-1) is Governed by an Activated Glutamate Dehydrogenase Diabetes  2018 Mar;67(3):372-384 .

The stimulation of GLP-1 secretion and delivery of GLP-1 agonists via nanostructured lipid carriers Nanoscale. 2018 Jan 3;10(2):603-613

Boarfish (Capros aper) protein hydrolysate has potent insulinotropic and GLP-1 secretory activity in vitro and acute glucose lowering effects in mice. Int J Food Sci Technol, 2019 54: 271-281. doi:10.1111/ijfs.13975

Size Effect on Lipid Nanocapsule-Mediated GLP-1 Secretion from Enteroendocrine L Cells Mol Pharm. 2018 Jan 2;15(1):108-115

YH18968, a Novel 1,2,4-Triazolone G-Protein Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes Mellitus Biomol Ther (Seoul). 2018 Mar 1;26(2):201-209

INSL5 activates multiple signalling pathways and regulates GLP-1 secretion in NCI-H716 cells J Mol Endocrinol. 2018 Apr;60(3):213-224

α7 Nicotinic Acetylcholine Receptor Regulates the Function and Viability of L Cells Endocrinology. 2018 Sep 1;159(9):3132-3142

Atlantic salmon (Salmo salar) co-product-derived protein hydrolysates: A source of antidiabetic peptides Food Res Int. 2018 Apr;106:598-606

Blue whiting (Micromesistius poutassou) muscle protein hydrolysate with in vitro and in vivoantidiabetic properties Journal of functional foods January 2018 https://doi.org/10.1016/j.jff.2017.10.045

17-β Estradiol regulates proglucagon-derived peptide secretion in mouse and human α- and L cells JCI Insight. 2018 Apr 5;3(7). pii: 98569. doi: 10.1172/jci.insight.98569

Intestinal CART is a regulator of GIP and GLP-1 secretion and expression Mol Cell Endocrinol. 2018 Apr 5. pii: S0303-7207(18)30121-7

Bitter tastant quinine modulates glucagon-like peptide-1 exocytosis from clonal GLUTagenteroendocline L cells via actin reorganization Biochem Biophys Res Commun. 2018 Apr 20. pii: S0006-291X(18)30924-0

Wheat gluten hydrolysate potently stimulates peptide-YY secretion and suppresses food intake in rats Biosci Biotechnol Biochem.2018 Nov;82(11):1992-1999

Bacterial metabolite S-equol modulates glucagon-like peptide-1 secretion from enteroendocrine L cell line GLUTag cells  Biochem Biophys Res Commun. 2018 May 16. pii: S0006-291X(18)31163-X

Murine GLUTag Cells The Impact of Food Bioactives on Health: in vitro and ex vivo models [Internet]. Cham (CH): Springer; 2015. Chapter 21

Intestinal enteroendocrine L cells in amino acid sensing and diseases [Frontiers In Bioscience, Landmark, 23, 1740-1753, March 1, 2018] 

Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119 Biochim Biophys Acta. 2018 Jun 5. pii: S1388-1981(18)30128-8

Acute and Repeated Treatment with 5-PAHSA or 9-PAHSA Isomers Does Not Improve Glucose Control in Mice Cell Metab. 2018 Jun 15. pii: S1550-4131(18)30381-4

Farnesoid X Receptor (FXR) Interacts with Camp Response Element Binding Protein (CREB) to Modulate Glucagon-Like Peptide-1 (7-36) Amide (GLP-1) Secretion by Intestinal L Cell Cell Physiol Biochem. 2018 Jun 21;47(4):1442-1452

Acute administration of interleukin-6 does not increase secretion of glucagon-like peptide-1 in mice Physiol Rep. 2018 Jul;6(13):e13788. doi: 10.14814/phy2.13788

Chronic Exposure to Palmitate Impairs Insulin Signaling in an Intestinal L-cell Line: A Possible Shift from GLP-1 to Glucagon Production Int J Mol Sci. 2018 Nov 28;19(12).

Oleate increase neutral lipid accumulation, cellular respiration and rescues palmitate-exposed GLP 1  secreting  cells by reducing ceramide-induced ROS Biochimie 2018 Dec 1. pii: S0300-9084(18)30342-0. doi: 10.1016/j.biochi.2018.11.017

Casein materials show different digestion patterns using an in vitro gastrointestinal model and different release of glucagon-like peptide-1 by enteroendocrine GLUTag cells Food Chem. 2019 Mar 30;277:423-431.

HM47118A, a novel insulinotropic GPR119 agonist and potential oral antidiabetic agent Diabetes Res Clin Pract. 2019 Jan 11. pii: S0168-8227(18)31385-8

Discovery of ((1,2,4-oxadiazol-5-yl)pyrrolidin-3-yl)ureidyl derivatives as selective non-steroidal agonists of the G-protein coupled bile acid receptor-1 Sci Rep 2019 Feb 21;9(1):2504. doi: 10.1038/s41598-019-38840-z

Zinc-induced activation of GPR39 regulates glucose homeostasis through glucose-dependent insulinotropic polypeptide secretion from enteroendocrine K-cells Biol Chem. 2018 Dec 1. pii: /j/bchm.just-accepted/hsz-2018-0393/hsz-2018-0393.xml. doi: 10.1515/hsz-2018-0393

Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinalenterocytes and afferent neurons Nat Commun 2019 Mar 4;10(1):1029. doi: 10.1038/s41467-019-09045-9

Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism FASEB J. 2019 Apr 2:fj201801526RR. doi: 10.1096/fj.201801526RR

SCO-267, a GPR40 full agonist, improves glycemic and body weight control in rat models of diabetes and obesity

J Pharmacol Exp Ther. 2019 Jun 10. pii: jpet.118.255885. 

The apoptosis and GLP-1 hyposecretion induced by LPS via RIP/ROS/mTOR pathway in GLUTag cells. Biochimie. 2019 Jul;162:229-238

Oleate increase neutral lipid accumulation, cellular respiration and rescues palmitate-exposed GLP-1 secreting cells by reducing ceramide-induced ROS Biochimie. 2019 Apr;159:23-35

Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1 Obesity (Silver Spring). 2019 Aug;27(8):1292-1304

Chronic treatment of JTP-109192, a novel G-protein coupled receptor 119 agonist, improves metabolic abnormalities in Zucker Fatty rats Clin Exp Pharmacol Physiol. 2019 Aug 5. doi: 10.1111/1440-1681.13152 

Novel strategy for oral peptide delivery in incretin-based diabetes treatment Gut. 2019 Aug 10. pii: gutjnl-2019-319146. doi

Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids Nature Communications  2019 10 , 1–15

The core clock gene, Bmal1, and its downstream target, the SNARE regulatory protein secretagogin, are necessary for circadian secretion of glucagon-like peptide-1 Mol Metabolism 2019 https://doi.org/10.1016/j.molmet.2019.11.004

Novel GPR120 agonist TUG891 modulates fat taste perception and preference and activates tongue-brain-gut axis in mice J Lipid Res. 2019 Dec 5. pii: jlr.RA119000142.

Inorganic mesoporous particles for controlled α-linolenic acid delivery to stimulate GLP-1 secretion in vitro Eur J Pharm Biopharm. 2019 Nov;144:132-138.

Let-7e-5p regulates GLP-1 content and basal release from enteroendocrine L cells from DIO male mice Endocrinology. 2020 Jan 7. pii: bqz037. doi: 10.1210/endocr/bqz037

The nuclear receptor FXR inhibits Glucagon-Like Peptide-1 secretion in response to microbiota-derived Short-Chain Fatty Acids Sci Rep. 2020 Jan 13;10(1):174. doi: 10.1038/s41598-019-56743-x.

Glutamine-induced signaling pathways via amino acid receptors in enteroendocrine L cell line J Mol Endocrinol. 2020 Jan 1. pii: JME-19-0260.R1. doi: 10.1530/JME-19-0260

Flavone Hispidulin Stimulates Glucagon-Like peptide-1 Secretion and Ameliorates Hyperglycemia in Streptozotocin-Induced Diabetic Mice Mol Nutr Food Res. 2020 Jan 21:e1900978

Glucagon receptor antagonist upregulates circulating GLP-1 level by promoting intestinal L-cell proliferation and GLP-1 production in type 2 diabetes BMJ Open Diabetes Res Care. 2020 Mar;8(1). pii: e001025. doi: 10.1136/bmjdrc-2019-00102

Inhibition of hepatic bile acid uptake by Myrcludex B promotes glucagon-like peptide 1 release and reduces obesity

Cell Mol Gastroenterol Hepatol. 2020 Apr 21. pii: S2352-345X(20)30053-9

ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment Int J Mol Sci. 2020 May 28;21(11):E3824

Silychristin A Activates Nrf2-HO-1/SOD2 Pathway to Reduce Apoptosis and Improve GLP-1 Production Through Upregulation of Estrogen Receptor α in GLUTag Cells Eur J Pharmacol 2020 Jun 1;173236. doi: 10.1016/j.ejphar.2020.173236.

Kaempferol in ameliorating diabetes-induced fibrosis and renal damage: An in vitro and in vivo study in diabetic nephropathy mice model Phytomedicine. 2020 May 16;76:153235. doi: 10.1016/j.phymed.2020.153235

Effects of active farnesoid X receptor on GLUTag enteroendocrine L cells Mol Cell Endocrinol. 2020 Nov 1;517:110923. doi: 10.1016/j.mce.2020.110923

Dipeptidyl peptidase-4 and GLP-1 interplay in STC-1 and GLUTag cell lines Peptides. 2020 Dec;1

34:170419. doi: 10.1016/j.peptides.2020.170419

Interleukin-1β Suppresses Gastrin via Primary Cilia and Induces Antral Hyperplasia Cell Mol Gastroenterol Hepatol. 2021;11(5):1251-1266.

Epicatechin and Anthocyanins Modulate GLP-1 Metabolism: Evidence from C57BL/6J Mice and GLUTag Cells

Nutr. 2021 Jun 1;151(6):1497-1506. doi: 10.1093/jn/nxab029

Macroalgal protein hydrolysates from Palmaria palmata influence the 'incretin effect' in vitro via DPP-4 inhibition and upregulation of insulin, GLP-1 and GIP secretion Eur J Nutr. 2021 Jun 3. doi: 10.1007/s00394-021-02583-3.

Isoprenoid Derivatives of Lysophosphatidylcholines Enhance Insulin and GLP-1 Secretion through Lipid-Binding GPCRs Int J Mol Sci. 2021 May 27;22(11):5748

Dynamin regulates L cell secretion in human gut Mol Cell Endocrinol. 2021 Sep 15;535:111398. doi: 10.1016/j.mce.2021.111398.

(E)-7-Ethylidene-lithocholic Acid (7-ELCA) Is a Potent Dual Farnesoid X Receptor (FXR) Antagonist and GPBAR1 Agonist Inhibiting FXR-Induced Gene Expression in Hepatocytes and Stimulating Glucagon-like Peptide-1 Secretion From Enteroendocrine Cells Front Pharmacol. 2021 Aug 13;12:713149.

L-cell Arntl is required for rhythmic glucagon-like peptide-1 secretion and maintenance of intestinal homeostasis

Mol Metab. 2021 Sep 11:101340. doi: 10.1016/j.molmet.2021.101340

Mulberry leaves ameliorate diabetes via regulating metabolic profiling and AGEs/RAGE and p38 MAPK/NF-κB pathway J Ethnopharmacol. 2022 Jan 30;283:114713.

Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation Gut Microbes. 2021 Jan-Dec;13(1):1987782

Identification of G protein-coupled receptor 55 (GPR55) as a target of curcumin NPJ Sci Food. 2022 Jan 14;6(1):4. doi: 10.1038/s41538-021-00119-x.

Silibinin improves L-cell mass and function through an estrogen receptor-mediated antioxidative mechanism Phytomedicine. 2022 Feb 27;99:154022. 

Glucagon-like Peptide-1 Secretion Is Inhibited by Lysophosphatidic Acid Int J Mol Sci. 2022 Apr 9;23(8):4163.

Intestinal Gpr17 deficiency improves glucose metabolism by promoting GLP-1 secretion Cell Rep. 2022 Jan 4;38(1):110179.

Nobiletin ameliorates high fat-induced disruptions in rhythmic glucagon-like peptide-1 secretion Sci Rep. 2022 May 4;12(1):7271

NMDA Receptor Antagonists Increase the Release of GLP-1 From Gut Endocrine Cells Front Pharmacol. 2022 Apr 27;13:861311.

Novel luciferase-based GLP-1 reporter assay reveals naturally-occurring secretagogues Br J Pharmacol. 2022 Jun 23. doi: 10.1111/bph.15896

Chlorogenic Acid: a Polyphenol from Coffee Rendered Neuroprotection Against Rotenone-Induced Parkinson's Disease by GLP-1 Secretion Mol Neurobiol. 2022 Nov;59(11):6834-6856

Consumption of barley flour increases gut fermentation and improves glucose intolerance via the short-chain fatty acid receptor GPR43 in obese male mice Food Funct. 2022 Oct 31;13(21):10970-10980.

F-actin determines the time-dependent shift in docking dynamics of glucagon-like peptide-1 granules upon stimulation of secretion FEBS Lett. 2023 Mar;597(5):657-671. doi: 10.1002/1873-3468.14580

Incretins play an important role in FFA4/GPR120 regulation of glucose metabolism by GW-9508 Life Sci. 2023 Apr 1;318:121475. doi: 10.1016/j.lfs.2023.121475.

βHB inhibits glucose-induced GLP-1 secretion in GLUTag and human jejunal enteroids J Mol Endocrinol. 2023 Feb 1:JME-22-0115. doi: 10.1530/JME-22-0115

Wei-Tong-Xin exerts anti-inflammatory effects through TLR4-mediated macrophages M1/M2 polarization and affects GLP-1 secretion J Pharma Pharmacol 2023 Mar 7;rgad014. doi: 10.1093/jpp/rgad014