GPR40 agonists for the treatment of type 2 diabetes: life after ‘TAKing’ a hit

GPR40 (FFAR1) – Combined Gs and Gq signaling in vitro is associated with robust incretin secretagogue action ex vivo and in vivo

(2015) Maria Hauge et al.   Molecular Metabolism

Increased Glucose Metabolism and Glycerolipid Formation by Fatty Acids and GPR40 Receptor Signaling Underlies the Fatty Acid Potentiation of Insulin Secretion

(2014) Mahmoud El-Azzouny et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875

(2014) Ankita Srivastava et al.   NATURE

Lead GPR40 agonist bites the dust

(2014)   NATURE REVIEWS DRUG DISCOVERY

Optimization of GPR40 Agonists for Type 2 Diabetes

(2014) Jiwen (Jim) Liu et al.   ACS Medicinal Chemistry Letters

CNX-011-67, a novel GPR40 agonist, enhances glucose responsiveness, insulin secretion and islet insulin content in n-STZ rats and in islets from type 2 diabetic patients

(2014) Venkategowda Sunil et al.   BMC Pharmacology & Toxicology

Fatty Acid Receptor Gpr40 Mediates Neuromicrovascular Degeneration Induced by Transarachidonic Acids in Rodents

(2013) Jean-Claude Honoré et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Metabolic Signaling in Fuel-Induced Insulin Secretion

(2013) Marc Prentki et al.   Cell Metabolism

Recent developments in biased agonism

(2013) James W Wisler et al.   CURRENT OPINION IN CELL BIOLOGY

Reevaluation of Fatty Acid Receptor 1 as a Drug Target for the Stimulation of Insulin Secretion in Humans

(2013) R. Wagner et al.   DIABETES

FFAR1 Is Involved in Both the Acute and Chronic Effects of Palmitate on Insulin Secretion

(2013) Hjalti Kristinsson et al.   ENDOCRINOLOGY

The Free Fatty Acid Receptor G Protein-coupled Receptor 40 (GPR40) Protects from Bone Loss through Inhibition of Osteoclast Differentiation

(2013) Fabien Wauquier et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Activation of FFA1 mediates GLP-1 secretion in mice. Evidence for allosterism at FFA1

(2013) Yumei Xiong et al.   MOLECULAR AND CELLULAR ENDOCRINOLOGY

DC260126: A Small-Molecule Antagonist of GPR40 that Protects against Pancreatic β-Cells Dysfunction in db/db Mice

(2013) Peng Sun et al.   PLoS One

A Novel Antidiabetic Drug, Fasiglifam/TAK-875, Acts as an Ago-Allosteric Modulator of FFAR1

(2013) Chiori Yabuki et al.   PLoS One

Hypothalamic GPR40 Signaling Activated by Free Long Chain Fatty Acids Suppresses CFA-Induced Inflammatory Chronic Pain

(2013) Kazuo Nakamoto et al.   PLoS One

The fatty acid receptor FFA1/GPR40 a decade later: how much do we know?

(2013) Arturo D. Mancini et al.   TRENDS IN ENDOCRINOLOGY AND METABOLISM

Discovery of TUG-770: A Highly Potent Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist for Treatment of Type 2 Diabetes

(2013) Elisabeth Christiansen et al.   ACS Medicinal Chemistry Letters

Discovery and Optimization of Potent GPR40 Full Agonists Containing Tricyclic Spirocycles

(2013) Yingcai Wang et al.   ACS Medicinal Chemistry Letters

Treatment with CNX-011-67, a novel GPR40 agonist, delays onset and progression of diabetes and improves beta cell preservation and function in male ZDF rats

(2013) Nagesh Gowda et al.   BMC Pharmacology & Toxicology

A Multiple-Ascending-Dose Study to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of a Novel GPR40 Agonist, TAK-875, in Subjects With Type 2 Diabetes

(2012) E Leifke et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Randomized, Double-Blind, Dose-Ranging Study of TAK-875, a Novel GPR40 Agonist, in Japanese Patients With Inadequately Controlled Type 2 Diabetes

(2012) K. Kaku et al.   DIABETES CARE

G protein-coupled receptor (GPR)40-dependent potentiation of insulin secretion in mouse islets is mediated by protein kinase D1

(2012) M. Ferdaoussi et al.   DIABETOLOGIA

Thiazolidinediones Induce Osteocyte Apoptosis by a G Protein-coupled Receptor 40-dependent Mechanism

(2012) Aleksandra Mieczkowska et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial

(2012) Charles F Burant et al.   LANCET

GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus

(2012) Juris J. Meier   Nature Reviews Endocrinology

A Potent Class of GPR40 Full Agonists Engages the EnteroInsular Axis to Promote Glucose Control in Rodents

(2012) Jian Luo et al.   PLoS One

Bridging the gap: bitopic ligands of G-protein-coupled receptors

(2012) J. Robert Lane et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Molecular Mechanism of β-Arrestin-Biased Agonism at Seven-Transmembrane Receptors

(2011) Eric Reiter et al.   Annual Review of Pharmacology and Toxicology

Involvement of the long-chain fatty acid receptor GPR40 as a novel pain regulatory system

(2011) Kazuo Nakamoto et al.   BRAIN RESEARCH

New insights into “GPR40-CREB interaction inadult neurogenesis” specific for primates

(2011) Nadezhda B. Boneva et al.   HIPPOCAMPUS

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Properties of the GPR40 Agonist TAK-875: Results From a Double-Blind, Placebo-Controlled Single Oral Dose Rising Study in Healthy Volunteers

(2011) Himanshu Naik et al.   JOURNAL OF CLINICAL PHARMACOLOGY

Acute stimulation of glucagon secretion by linoleic acid results from GPR40 activation and [Ca2+]i increase in pancreatic islet α-cells

(2011) Li Wang et al.   JOURNAL OF ENDOCRINOLOGY

Applying label-free dynamic mass redistribution technology to frame signaling of G protein–coupled receptors noninvasively in living cells

(2011) Ralf Schröder et al.   Nature Protocols

AMG 837: A Novel GPR40/FFA1 Agonist that Enhances Insulin Secretion and Lowers Glucose Levels in Rodents

(2011) Daniel C.-H. Lin et al.   PLoS One

DC260126, a small-molecule antagonist of GPR40, improves insulin tolerance but not glucose tolerance in obese Zucker rats

(2010) Xiaodong Zhang et al.   BIOMEDICINE & PHARMACOTHERAPY

Glucolipotoxicity age-dependently impairs beta cell function in rats despite a marked increase in beta cell mass

(2010) G. Fontés et al.   DIABETOLOGIA

The G-Protein−Coupled Receptor GPR40 Directly Mediates Long-Chain Fatty Acid−Induced Secretion of Cholecystokinin

(2010) Alice P. Liou et al.   GASTROENTEROLOGY

The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice

(2010) Antonia Sassmann et al.   JOURNAL OF CLINICAL INVESTIGATION

Taste Preference for Fatty Acids Is Mediated by GPR40 and GPR120

(2010) C. Cartoni et al.   JOURNAL OF NEUROSCIENCE

GPR40 is partially required for insulin secretion following activation of β3-adrenergic receptors

(2010) Zhen Pang et al.   MOLECULAR AND CELLULAR ENDOCRINOLOGY

Therapeutic potential of β-arrestin- and G protein-biased agonists

(2010) Erin J. Whalen et al.   TRENDS IN MOLECULAR MEDICINE

Glucolipotoxicity of the pancreatic beta cell

(2009) Vincent Poitout et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS

Deletion of GPR40 Impairs Glucose-Induced Insulin Secretion In Vivo in Mice Without Affecting Intracellular Fuel Metabolism in Islets

(2009) T. Alquier et al.   DIABETES

GPR40: Good Cop, Bad Cop?

(2009) T. Alquier et al.   DIABETES

Overexpression of GPR40 in Pancreatic  -Cells Augments Glucose-Stimulated Insulin Secretion and Improves Glucose Tolerance in Normal and Diabetic Mice

(2009) K. Nagasumi et al.   DIABETES

Mechanisms of biphasic insulin-granule exocytosis - roles of the cytoskeleton, small GTPases and SNARE proteins

(2009) Z. Wang et al.   JOURNAL OF CELL SCIENCE

G-protein-coupled receptor 40 (GPR40) expression and its regulation in human pancreatic islets: The role of type 2 diabetes and fatty acids

(2009) S. Del Guerra et al.   NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES

Selective Small-Molecule Agonists of G Protein-Coupled Receptor 40 Promote Glucose-Dependent Insulin Secretion and Reduce Blood Glucose in Mice

(2008) C. P. Tan et al.   DIABETES

The Fatty Acid Receptor GPR40 Plays a Role in Insulin Secretion In Vivo After High-Fat Feeding

(2008) M. Kebede et al.   DIABETES

Lack of FFAR1/GPR40 Does Not Protect Mice From High-Fat Diet-Induced Metabolic Disease

(2008) H. Lan et al.   DIABETES

Gpr40 Is Expressed in Enteroendocrine Cells and Mediates Free Fatty Acid Stimulation of Incretin Secretion

(2008) S. Edfalk et al.   DIABETES

Nutrient-dependent secretion of glucose-dependent insulinotropic polypeptide from primary murine K cells

(2008) H. E. Parker et al.   DIABETOLOGIA

Modulation of Osteoclastogenesis by Fatty Acids

(2008) Jillian Cornish et al.   ENDOCRINOLOGY

Activation of ATP-sensitive potassium channels in rat pancreatic β-cells by linoleic acid through both intracellular metabolites and membrane receptor signalling pathway

(2008) Yu-Feng Zhao et al.   JOURNAL OF ENDOCRINOLOGY

Production and characterization of a monoclonal antibody against GPR40 (FFAR1; free fatty acid receptor 1)

(2007) Akira Hirasawa et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Expression of free fatty acid receptor GPR40 in the neurogenic niche of adult monkey hippocampus

(2007) Dexuan Ma et al.   HIPPOCAMPUS