Oligopeptides stimulate glucagon-like peptide-1 secretion in mice through proton-coupled uptake and the calcium-sensing receptor.

Diakogiannaki E, Pais R, Tolhurst G, Parker HE, Horscroft J, Rauscher B, Zietek T, Daniel H, Gribble FM, Reimann F.
Journal   Diabetologia
Species  
Analytes Measured   GLP-1
Matrix Tested   Cell culture supernatnants, cell lysates
Year   2013
Volume  
Page Numbers  
Application   Metabolic
Abstract
AIMS/HYPOTHESIS: Ingested protein is a well-recognised stimulus for glucagon-like peptide-1 (GLP-1) release from intestinal L cells. This study aimed to characterise the molecular mechanisms employed by L cells to detect oligopeptides.

METHODS: GLP-1 secretion from murine primary colonic cultures and Ca2+ dynamics in L cells were monitored in response to peptones and dipeptides. L cells were identified and purified based on their cell-specific expression of the fluorescent protein Venus, using GLU-Venus transgenic mice. Pharmacological tools and knockout mice were used to characterise candidate sensory pathways identified by expression analysis.

RESULTS: GLP-1 secretion was triggered by peptones and di-/tripeptides, including the non-metabolisable glycine-sarcosine (Gly-Sar). Two sensory mechanisms involving peptide transporter-1 (PEPT1) and the calcium-sensing receptor (CaSR) were distinguishable. Responses to Gly-Sar (10 mmol/l) were abolished in the absence of extracellular Ca2+ or by the L-type calcium-channel blocker nifedipine (10 μmol/l) and were PEPT1-dependent, as demonstrated by their sensitivity to pH and 4-aminomethylbenzoic acid and the finding of impaired responses in tissue from Pept1 (also known as Slc15a1) knockout mice. Peptone (5 mg/ml)-stimulated Ca2+ responses were insensitive to nifedipine but were blocked by antagonists of CaSR. Peptone-stimulated GLP-1 secretion was not impaired in mice lacking the putative peptide-responsive receptor lysophosphatidic acid receptor 5 (LPAR5; also known as GPR92/93).

CONCLUSIONS/INTERPRETATION: Oligopeptides stimulate GLP-1 secretion through PEPT1-dependent electrogenic uptake and activation of CaSR. Both pathways are highly expressed in native L cells, and likely contribute to the ability of ingested protein to elevate plasma GLP-1 levels. Targeting nutrient-sensing pathways in L cells could be used to mobilise endogenous GLP-1 stores in humans, and could mimic some of the metabolic benefits of bariatric surgery.

View Publications

Related Products

U-PLEX Diabetes Combo 1 (mouse)
C-Peptide, GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) | Mouse
Multiplex
U-PLEX Metabolic 3-Plex Combo 1 (mouse)
GLP-1 (total), Glucagon, Insulin | Mouse
Multiplex
U-PLEX Diabetes Combo 1 (human)
C-Peptide, GIP (total), GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) | Human
Multiplex
U-PLEX Microbiome Combo 1 (human)
Ghrelin (total), GLP-1 (total), Glucagon, Insulin, Leptin, PP, PYY (total) | Human
Multiplex
U-PLEX Diabetes Combo 1 (rat)
C-Peptide, GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) | Rat
Multiplex
U-PLEX Metabolic 3-Plex Combo 1 (rat)
GLP-1 (total), Glucagon, Insulin | Rat
Multiplex
U-PLEX Custom Metabolic Group 1 (rat) 384-well Assays
Rat
Multiplex
U-PLEX Mouse GLP-1 (total) 384-Well Assay
GLP-1 (total) | Mouse
Singleplex
U-PLEX Rat GLP-1 (total) 384-Well Assay
GLP-1 (total) | Rat
Singleplex
U-PLEX Custom Metabolic Group 1 (mouse) 384-well Assays
BAFF, BCA-1/BLC, BDNF, CD40/TNFRSF5, C-Peptide, Eotaxin, EPO, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, IFN-α, IFN-β, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, Insulin, IP-10, KC/GRO, Leptin, MCP-1, MCP-5/CCL12, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α, MMP-9 (total), PYY (total), RANTES, TARC, TNF-α, VEGF-A | Mouse
Multiplex
U-PLEX Custom Metabolic Group 1 (human) 384-well Assays
BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 | Human
Multiplex
U-PLEX Human GLP-1 (total) 384-well Assay
GLP-1 (total) | Human
Singleplex
U-PLEX Human GLP-1 (total) Assay
GLP-1 (total) | Human
Singleplex
U-PLEX Mouse GLP-1 (total) Assay
GLP-1 (total) | Mouse
Singleplex
U-PLEX Rat GLP-1 (total) Assay
GLP-1 (total) | Rat
Singleplex
U-PLEX Custom Metabolic Group 1 (rat) Assays
Rat
Multiplex
U-PLEX Custom Metabolic Group 1 (mouse) Assays
Mouse
Multiplex
U-PLEX Metabolic Combo 1 (rat)
BDNF, C-Peptide, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) | Rat
Multiplex
U-PLEX Metabolic Combo 1 (mouse)
BAFF, BDNF, C-Peptide, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) | Mouse
Multiplex
U-PLEX Obesity Combo 2 (rat)
C-Peptide, Ghrelin (total), GLP-1 (total), Insulin, Leptin, PYY (total) | Rat
Multiplex
U-PLEX Obesity Combo 2 (mouse)
C-Peptide, Ghrelin (total), GLP-1 (total), Insulin, Leptin, PYY (total) | Mouse
Multiplex
U-PLEX Custom Metabolic Group 1 (human) Assays
BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 | Human
Multiplex
U-PLEX GLP-1 (total) Antibody Set (5 Plate Size)
GLP-1 (total) | Human, Mouse, Rat
U-PLEX Obesity Combo 2 (human)
C-Peptide, FGF-23, Ghrelin (total), GLP-1 (total), Insulin, Leptin, PYY (total) | Human
Multiplex
U-PLEX Metabolic Combo 1 (human)
BAFF, BDNF, β-NGF, C-Peptide, FGF-21, FGF-23, FSH, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, Insulin, Leptin, Luteinizing Hormone (LH), PP, Proinsulin, PYY (total) | Human
Multiplex
GLP-1 (total) Control Pack
GLP-1 (total) | Human, Mouse, Non-human primate, Rat, Canine
V-PLEX GLP-1 (total) Kit
GLP-1 (total) | Human, Mouse, Non-human primate, Rat, Canine
Singleplex
V-PLEX Plus GLP-1 (total) Kit
GLP-1 (total) | Human, Mouse, Non-human primate, Rat, Canine
Singleplex
GLP-1 (total) Antibody
GLP-1 (total) | Human
Browse Our Products

By Analytes
By Applications
Search
Customer Service/Orders


Scientific/Technical Support


Instrument Support


Company Headquarters