GSK256073, a selective agonist of G-protein coupled receptor 109A (GPR109A) reduces serum glucose in subjects with type 2 diabetes mellitus.

Dobbins RL, Shearn SP, Byerly RL, Gao FF, Mahar KM, Napolitano A, Nachbaur GJ, Le Monnier de Gouville AC.
Journal   Diabetes Obes Metab.
Species  
Analytes Measured   Insulin
Matrix Tested   Plasma
Year   2013
Volume  
Page Numbers  
Application   Metabolic
Abstract
AIMS: This clinical trial assessed whether a potent, selective GPR109A agonist, GSK256073, could, through inhibition of lipolysis, acutely improve glucose homeostasis in subjects with type 2 diabetes mellitus.

METHODS: Thirty-nine diabetic subjects were enrolled in the randomized, single-blind, placebo-controlled, three-period crossover trial. Each subject received placebo and two of four regimens of GSK256073 for 2 days. GSK256073 was dosed 5 mg every 12 h before breakfast and supper (BID), 10 mg every 24 h before breakfast (QD), 25 mg BID and 50 mg QD.

RESULTS: The change from baseline weighted mean glucose concentration for an interval from 24 to 48 h after the initial drug dose was significantly reduced for all GSK256073 regimens, reaching a maximum of -0.87 mmol/l (-1.20, -0.52) with the 25 mg BID dose. Sustained suppression of non-esterified fatty acid (NEFA) and glycerol concentrations was observed with all GSK256073 doses throughout the 48-h dosing period. Serum insulin and C-peptide concentrations fell in concert with glucose concentrations and calculated HOMA-IR scores decreased 27-47%, consistent with insulin sensitization. No marked differences were evident between either 10 and 50 mg total daily doses or QD versus BID dosing.

CONCLUSIONS: Administration of a GPR109A agonist for 2 days significantly decreased serum NEFA and glucose concentrations in diabetic subjects. Glucose improvements were associated with decreased insulin concentrations and measures of enhanced insulin sensitivity. Improved glucose control occurred with GSK256073 doses that were generally safe and not associated with events of flushing or gastrointestinal disturbances.

View Publications

Related Products

Human Insulin Kit
Insulin | Human
Singleplex
U-PLEX Custom Metabolic Group 1 (hu) 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 Metabolic Group 1 (hu) 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
U-PLEX Adipokine Combo 1 (hu)
BDNF, β-NGF, IL-1β, IL-6, IL-8, IL-10, Insulin, Leptin, MCP-1, TNF-α | Human
Multiplex
U-PLEX Diabetes Combo 1 (hu)
C-Peptide, GIP (total), GLP-1 (total), Glucagon, Insulin, Leptin, PYY (total) | Human
Multiplex
U-PLEX Diabetes Combo 2 (hu)
C-Peptide, GIP (total), GLP-1 (active), Glucagon, Insulin, Leptin, PYY (total) | Human
Multiplex
U-PLEX Human Insulin Assay
Insulin | Human
Singleplex
U-PLEX Metabolic Combo 1 (hu)
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
U-PLEX Obesity Combo 2 (hu)
C-Peptide, FGF-23, Ghrelin (total), GLP-1 (total), Insulin, Leptin, PYY (total) | Human
Multiplex
U-PLEX Human Insulin Antibody Set
Insulin | Human
R-PLEX Insulin Antibody Set
Insulin | Human
Singleplex
Human Active GLP-1(7-36)amide, Insulin, Glucagon, Leptin Kit
GLP-1 (active), Glucagon, Insulin, Leptin | Human
Multiplex
Human Active GLP-1, Insulin, Glucagon, Leptin Kit
GLP-1 (active), Glucagon, Insulin, Leptin | Human
Multiplex
Human GLP-1(7-36)amide, Glucagon, Insulin Kit
GLP-1 (active), Glucagon, Insulin | Human
Multiplex
Human Leptin, Insulin Kit
Insulin, Leptin | Human
Multiplex
Mouse/Rat Insulin, Glucagon Kit
Glucagon, Insulin | Mouse, Rat
Multiplex
Mouse Metabolic Kit
Insulin, Leptin | Mouse
Multiplex
Mouse/Rat GLP-1 (7-36)amide, Glucagon, Insulin Kit
GLP-1 (total), Glucagon, Insulin | Mouse, Rat
Multiplex
Mouse/Rat Insulin Kit
Insulin | Mouse, Rat
Singleplex
Mouse/Rat Active GLP-1 (7-36)amide, Insulin, Glucagon Kit
GLP-1 (total), Glucagon, Insulin | Mouse, Rat
Multiplex
Mouse/Rat Total Active GLP-1, Insulin, Glucagon Kit
GLP-1 (total), Glucagon, Insulin | Mouse, Rat
Multiplex
Rat Leptin, Insulin Kit
Insulin, Leptin | Rat
Multiplex
Browse Our Products

By Analytes
By Applications
Search
Customer Service/Orders


Scientific/Technical Support


Instrument Support


Company Headquarters