The FFA receptor GPR40 links hyperinsulinemia, hepatic steatosis, and impaired glucose homeostasis in mouse.

No abstract is available for this paper.

• Publication year

  2005

• Venue

  Cell Metabolism

• Publication date

  2005-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/J.CMET.2005.03.007PMID 16054069
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Metabolic syndrome: a clinical and molecular perspective.

  2005cited by this paper
• Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120

  2005cited by this paper
• Angiotensin II type 1 receptor overexpression in podocytes induces glomerulosclerosis in transgenic rats.

  2004cited by this paper
• The Glucocorticoid-induced Gene tdag8 Encodes a Pro-apoptotic G Protein-coupled Receptor Whose Activation Promotes Glucocorticoid-induced Apoptosis*

  2004cited by this paper
• PPARs and the complex journey to obesity

  2004cited by this paper
• Rosiglitazone prevents the impairment of human islet function induced by fatty acids: evidence for a role of PPARgamma2 in the modulation of insulin secretion.

  2004cited by this paper
• Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes

  2004cited by this paper
• Biochemical Mechanism of Lipid-induced Impairment of Glucose-stimulated Insulin Secretion and Reversal with a Malate Analogue*

  2004cited by this paper
• Hepatic gene expression profiles in a long-term high-fat diet-induced obesity mouse model.

  2004cited by this paper
• The Orphan G Protein-coupled Receptor GPR40 Is Activated by Medium and Long Chain Fatty Acids*

  2003cited by this paper
• A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs.

  2003cited by this paper
• Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes.

  2003cited by this paper
• Adipocyte-specific Gene Expression and Adipogenic Steatosis in the Mouse Liver Due to Peroxisome Proliferator-activated Receptor γ1 (PPARγ1) Overexpression*

  2003cited by this paper
• A sustained increase in plasma free fatty acids impairs insulin secretion in nondiabetic subjects genetically predisposed to develop type 2 diabetes.

  2003cited by this paper
• Liver Peroxisome Proliferator-activated Receptor γ Contributes to Hepatic Steatosis, Triglyceride Clearance, and Regulation of Body Fat Mass*

  2003cited by this paper
• Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40

  2003cited by this paper
• The physiology of cellular liporegulation.

  2003cited by this paper
• Pleiotropic effects of fatty acids on pancreatic β‐cells

  2003cited by this paper
• Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor gamma1 (PPARgamma1) overexpression.

  2003cited by this paper
• Variation in type 2 diabetes--related traits in mouse strains susceptible to diet-induced obesity.

  2003cited by this paper
• Fatty acid metabolism and insulin secretion in pancreatic beta cells

  2003cited by this paper
• Pleiotropic effects of fatty acids on pancreatic beta-cells.

  2003cited by this paper
• PPARalpha suppresses insulin secretion and induces UCP2 in insulinoma cells.

  2002cited by this paper
• Induction of Uncoupling Protein 2 mRNA in β-Cells Is Stimulated by Oxidation of Fatty Acids But Not by Nutrient Oversupply.

  2002cited by this paper
• Fatty acid transport: the roads taken.

  2002cited by this paper
• PPARα suppresses insulin secretion and induces UCP2 in insulinoma cells

  2002cited by this paper
• Overexpression of Dominant-Negative Mutant Hepatocyte Nuclear Factor-1α in Pancreatic β-Cells Causes Abnormal Islet Architecture With Decreased Expression of E-Cadherin, Reduced β-cell Proliferation, and Diabetes

  2002cited by this paper
• Pancreatic β-cell growth and survival – a role in obesity-linked type 2 diabetes?

  2002cited by this paper
• Pancreatic beta-cell growth and survival--a role in obesity-linked type 2 diabetes?

  2002cited by this paper
• Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver.

  2002cited by this paper
• Adenovirus-mediated overexpression of liver carnitine palmitoyltransferase I in INS1E cells: effects on cell metabolism and insulin secretion.

  2002cited by this paper
• Overexpression of dominant-negative mutant hepatocyte nuclear fctor-1 alpha in pancreatic beta-cells causes abnormal islet architecture with decreased expression of E-cadherin, reduced beta-cell proliferation, and diabetes.

  2002cited by this paper
• Role of ATP production and uncoupling protein-2 in the insulin secretory defect induced by chronic exposure to high glucose or free fatty acids and effects of peroxisome proliferator-activated receptor-gamma inhibition.

  2002cited by this paper
• Metabolic consequence of long-term exposure of pancreatic beta cells to free fatty acid with special reference to glucose insensitivity.

  2002cited by this paper
• Diet-induced obesity and hepatic gene expression alterations in C57BL/6J and ICAM-1-deficient mice.

  2002cited by this paper
• Induction of uncoupling protein 2 mRNA in beta-cells is stimulated by oxidation of fatty acids but not by nutrient oversupply.

  2002cited by this paper
• Effects of free fatty acids on insulin secretion in obesity

  2002cited by this paper
• Uncoupling protein 2: a possible link between fatty acid excess and impaired glucose-induced insulin secretion?

  2001cited by this paper
• Increased uncoupling protein-2 levels in beta-cells are associated with impaired glucose-stimulated insulin secretion: mechanism of action.

  2001cited by this paper
• Hepatic over-expression of peroxisome proliferator activated receptor γ2 in the ob/ob mouse model of non‐insulin dependent diabetes mellitus

  2001cited by this paper
• Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes.

  2001cited by this paper
• Diabetic KKAy mice exhibit increased hepatic PPARgamma1 gene expression and develop hepatic steatosis upon chronic treatment with antidiabetic thiazolidinediones.

  2001cited by this paper
• Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones.

  2000cited by this paper
• Attenuation of FGF signalling in mouse β-cells leads to diabetes

  2000cited by this paper
• Up-Regulation of Peroxisome Proliferator-Activated Receptors (PPAR-α) and PPAR-γ Messenger Ribonucleic Acid Expression in the Liver in Murine Obesity: Troglitazone Induces Expression of PPAR-γ-Responsive Adipose Tissue-Specific Genes in the Liver of Obese Diabetic Mice* * This work was supported by

  2000cited by this paper
• Up-regulation of peroxisome proliferator-activated receptors (PPAR-alpha) and PPAR-gamma messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-gamma-responsive adipose tissue-specific genes in the liver of obese diabetic mice.

  2000cited by this paper
• Attenuation of FGF signalling in mouse beta-cells leads to diabetes.

  2000cited by this paper
• Obesity and insulin resistance.

  2000cited by this paper
• Enhancing effects of long-term elevated glucose and palmitate on stored and secreted proinsulin-to-insulin ratios in human pancreatic islets.

  1999cited by this paper
• Lipid rather than glucose metabolism is implicated in altered insulin secretion caused by oleate in INS-1 cells.

  1999cited by this paper
• Glucose-fatty acid cycle to inhibit glucose utilization and oxidation is not operative in fatty acid-cultured islets.

  1999cited by this paper
• Deconstructing type 2 diabetes.

  1999cited by this paper
• Overexpression of uncoupling protein 2 inhibits glucose-stimulated insulin secretion from rat islets.

  1999cited by this paper
• Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity.

  1999cited by this paper
• Relative hyperproinsulinemia as a sign of islet dysfunction in women with impaired glucose tolerance.

  1999cited by this paper
• Long-term elevation of free fatty acids leads to delayed processing of proinsulin and prohormone convertases 2 and 3 in the pancreatic beta-cell line MIN6.

  1999cited by this paper
• Role of peroxisome proliferator-activated receptor α in disease of pancreatic β cells

  1998cited by this paper
• Overexpression of leptin receptors in pancreatic islets of Zucker diabetic fatty rats restores GLUT-2, glucokinase, and glucose-stimulated insulin secretion.

  1998cited by this paper
• Role of peroxisome proliferator-activated receptor alpha in disease of pancreatic beta cells.

  1998cited by this paper
• Type 2 Diabetes: When Insulin Secretion Fails to Compensate for Insulin Resistance

  1998cited by this paper
• Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression.

  1998cited by this paper
• Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreas.

  1997cited by this paper
• Total immunoreactive proinsulin, immunoreactive insulin and specific insulin in relation to conversion to NIDDM: the Mexico City Diabetes Study

  1997cited by this paper
• Dissociated insulinotropic sensitivity to glucose and carbachol in high-fat diet-induced insulin resistance in C57BL/6J mice.

  1997cited by this paper
• Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2

  1997cited by this paper
• Fatty Acids Rapidly Induce the Carnitine Palmitoyltransferase I Gene in the Pancreatic β-Cell Line INS-1*

  1997cited by this paper
• Making sense of glucose sensing

  1997cited by this paper
• Fatty Acids Decrease IDX-1 Expression in Rat Pancreatic Islets and Reduce GLUT2, Glucokinase, Insulin, and Somatostatin Levels*

  1997cited by this paper
• Fasting and decreased B cell sensitivity: important role for fatty acid-induced inhibition of PDH activity.

  1996cited by this paper
• Fasting proinsulin and 2-h post-load glucose levels predict the conversion to NIDDM in subjects with impaired glucose tolerance: The Hoorn Study

  1996cited by this paper
• Proinsulin as a Marker for the Development of NIDDM in Japanese-American Men

  1995cited by this paper
• Palmitate-induced beta-cell insensitivity to glucose is coupled to decreased pyruvate dehydrogenase activity and enhanced kinase activity in rat pancreatic islets.

  1995cited by this paper
• Overexpression of the Sky receptor tyrosine kinase at the cell surface or in the cytoplasm results in ligand-independent activation.

  1995cited by this paper
• Palmitate-Induced β-Cell Insensitivity to Glucose is Coupled to Decreased Pyruvate Dehydrogenase Activity and Enhanced Kinase Activity in Rat Pancreatic Islets

  1995cited by this paper
• Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle.

  1994cited by this paper

• Microbial-derived 3-phenylpropionic acid orchestrates immune-progenitor cell crosstalk to promote beige adipogenesis and energy expenditure.

  2026cites this paper
• Dynamics of Fatty Acid Composition in Lipids and Their Distinct Roles in Cardiometabolic Health

  2025cites this paper
• Free fatty acid receptors in GtoPdb v.2025.3

  2025cites this paper
• Single-cell mRNA-regulation analysis reveals cell type-specific mechanisms of type 2 diabetes

  2025cites this paper
• FOXA2 in islet biology: Orchestrating pancreatic development and glucose homeostasis

  2025cites this paper
• Bidirectional regulation of free fatty acid receptors and non-alcoholic fatty liver disease.

  2025cites this paper
• Role of fatty acids in the pathogenesis of ß-cell failure and Type-2 diabetes.

  2024cites this paper
• Lc—ms-based untargeted metabolomics reveals potential mechanisms of histologic chronic inflammation promoting prostate hyperplasia

  2024cites this paper
• Fatty acid esters of hydroxy fatty acids: A potential treatment for obesity‐related diseases

  2024cites this paper
• Exploring the Interplay between Fatty Acids, Inflammation, and Type 2 Diabetes

  2024cites this paper
• GPCRs involved in metabolic diseases: pharmacotherapeutic development updates

  2024cites this paper
• Unveiling sultam in drug discovery: spotlight on the underexplored scaffold.

  2024cites this paper
• The GPR40 novel agonist SZZ15‐11 improves non‐alcoholic fatty liver disease by activating the AMPK pathway and restores metabolic homeostasis in diet‐induced obese mice

  2024cites this paper
• Lipid Dynamics in Pancreatic β-Cells: Linking Physiology to Diabetes Onset

  2024cites this paper
• The Role of G Protein–Coupled Receptors and Receptor Kinases in Pancreatic β-Cell Function and Diabetes

  2024cites this paper
• Short-chain fatty acids (SCFAs) from gastrointestinal disorders, metabolism, epigenetics, central nervous system to cancer - A mini-review.

  2023cites this paper
• Glucose-stimulated insulin secretion depends on FFA1 and Gq in neonatal mouse islets

  2023cites this paper
• Free fatty acid receptors in GtoPdb v.2023.1

  2023cites this paper
• BRSK2 in pancreatic β cells promotes hyperinsulinemia-coupled insulin resistance and its genetic variants are associated with human type 2 diabetes

  2023cites this paper
• O304 ameliorates hyperglycemia in mice by dually promoting muscle glucose effectiveness and preserving β-cell function

  2023cites this paper
• Antioxidant Potential and Improvement Activities of Sterculia setigera Delile on Insulin Resistance in Type 2 Diabetic Rats Induced by High-Fat Diet and Low Dose of Streptozotocin

  2023cites this paper
• Loss of GPR40 in LDL receptor-deficient mice exacerbates high-fat diet-induced hyperlipidemia and nonalcoholic steatohepatitis

  2022cites this paper
• GPR40 Activation Abolishes Diabetes-Induced Painful Neuropathy by Suppressing VEGF-A Expression.

  2022cites this paper
• Expression and Functional Role of Olfactory, Taste, and Phototransduction Signal Proteins in β Cells in Islets of Langerhans

  2022cites this paper
• Could "cellular exercise" be the missing ingredient in a healthy life? Diets, caloric restriction, and exercise-induced hormesis.

  2022cites this paper
• Liver-derived metabolites as signaling molecules in fatty liver disease

  2022cites this paper
• Fatty Acid Transport and Signaling: Mechanisms and Physiological Implications.

  2022cites this paper
• Learn from failures and stay hopeful to GPR40, a GPCR target with robust efficacy, for therapy of metabolic disorders

  2022cites this paper
• Nutrient Sensing via Gut in Drosophila melanogaster

  2022cites this paper
• Involvement of Gut Microbial Metabolites Derived from Diet on Host Energy Homeostasis

  2022cites this paper
• Metabolic Transformation of Fat in Obesity Determines the Inflammation Resolving Capacity of Splenocardiac and Cardiorenal Networks in Heart Failure.

  2022cites this paper
• Short-Term Omega-3 Supplementation Modulates Novel Neurovascular and Fatty Acid Metabolic Proteome Changes in the Retina and Ophthalmic Artery of Mice with Targeted Cyp2c44 Gene Deletion

  2022cites this paper
• Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathway

  2022cites this paper
• CPL207280, a Novel G Protein–Coupled Receptor 40/Free Fatty Acid Receptor 1–Specific Agonist, Shows a Favorable Safety Profile and Exerts Antidiabetic Effects in Type 2 Diabetic Animals

  2021cites this paper
• – a novel GPR 40 / FFA 1-specific agonist shows a favorable safety profile and exerts anti-diabetic effects in type 2 diabetic animals

  2021cites this paper
• Novel advances in understanding fatty acid-binding G protein-coupled receptors and their roles in controlling energy balance.

  2021cites this paper
• Molecular mechanisms of lipotoxicity-induced pancreatic β-cell dysfunction.

  2021cites this paper
• Lipid-Induced Adaptations of the Pancreatic Beta-Cell to Glucotoxic Conditions Sustain Insulin Secretion

  2021cites this paper
• Impact of moderate exercise on fatty acid oxidation in pancreatic β-cells and skeletal muscle

  2021cites this paper
• Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells

  2021cites this paper
• Elucidation of the Physiological Functions of Membrane Proteins as Novel Drug Target Candidate Molecules.

  2021cites this paper
• Hydroxynonenal causes Langerhans cell degeneration in the pancreas of Japanese macaque monkeys

  2021cites this paper
• GPR40/FFA1 Free Fatty Acid Receptors and Their Functional Role

  2021cites this paper
• Pharmacology of Free Fatty Acid Receptors and Their Allosteric Modulators

  2021cites this paper
• Rhus chinensis Mill. Fruits Ameliorate Hepatic Glycolipid Metabolism Disorder in Rats Induced by High Fat/High Sugar Diet

  2021cites this paper
• Targeting lipid GPCRs to treat type 2 diabetes mellitus — progress and challenges

  2021cites this paper
• Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

  2021cites this paper
• GPR40/FFA1 Free Fatty Acid Receptors and Their Functional Role

  2021cites this paper
• Receptor Transduction Pathways Mediating Hormone Action

  2021cites this paper
• Targeting Enteroendocrine Cells to Treat Metabolic Disease

  2021cites this paper
• Free Fatty Acid Receptors as Mediators and Therapeutic Targets in Liver Disease

  2021cites this paper
• PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes

  2021cites this paper
• Free fatty acid receptor 1: a ray of hope in the therapy of type 2 diabetes mellitus

  2021cites this paper
• Naturally occurring mutations in G protein-coupled receptors associated with obesity and type 2 diabetes mellitus.

  2021cites this paper
• Connecting pancreatic islet lipid metabolism with insulin secretion and the development of type 2 diabetes

  2020cites this paper
• MANF AS A NEW REGULATOR OF THE UNFOLDED PROTEIN RESPONSE AND MAINTENANCE OF PANCREATIC β-CELLS IN MICE

  2020cites this paper
• Fenoxycarb and methoxyfenozide (RH-2485) affected development and chitin synthesis through disturbing glycometabolism in Lymantria dispar larvae.

  2020cites this paper
• Emerging roles of β-cell mitochondria in type-2-diabetes.

  2020cites this paper
• VEGF-B in islet of langerhans : role in vascular signaling and lipid handling

  2020cites this paper
• Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis

  2020cites this paper
• G protein-coupled receptors: Key molecules in metabolic associated fatty liver disease development.

  2020cites this paper
• GPCRs get Fatty: The Role of G Protein-Coupled Receptor Signaling in the Development and Progression of Nonalcoholic Fatty Liver Disease.

  2020cites this paper
• GPR40-Deficiency Is Associated with Hepatic FAT/CD36 Upregulation, Steatosis, Inflammation and Cell Injury in C57BL/6 Mice.

  2020cites this paper
• Evidence for NADPH oxidase activation by GPR40 in pancreatic β-cells

  2020cites this paper
• Therapeutic effect of Omega-3 fatty acids on T cell-mediated autoimmune diseases.

  2020cites this paper
• Short dietary intervention with olive oil increases brown adipose tissue activity in lean but not overweight subjects.

  2020cites this paper
• Free Fatty Acid Receptors in Health and Disease.

  2020cites this paper
• Dietary fat, salt, and sugar: a clinical perspective of the social catastrophe

  2020cites this paper
• Intermittent Fasting for Twelve Weeks Leads to Increases in Fat Mass and Hyperinsulinemia in Young Female Wistar Rats

  2020cites this paper
• Chronic activation of GPR40 does not negatively impact upon BRIN-BD11 pancreatic β-cell physiology and function

  2020cites this paper
• Title Long-Chain Free Fatty Acid Receptor GPR 120 Mediates Oil-Induced GIP Secretion Through CCK in Male Mice

  2019cites this paper
• The MAPK p38δ Regulate Glucose Homeostasis by Suppressing Insulin Secretion from Pancreatic β Cells

  2019cites this paper
• Involvement of G-Protein-Coupled Receptor 40 in the Inhibitory Effects of Docosahexaenoic Acid on SREBP1-Mediated Lipogenic Enzyme Expression in Primary Hepatocytes

  2019cites this paper
• Acute antinociceptive effect of fish oil or its major compounds, eicosapentaenoic and docosahexaenoic acids on diabetic neuropathic pain depends on opioid system activation.

  2019cites this paper
• Evaluation of GPR55 and GPR120 as novel therapeutic targets for the treatment of type 2 diabetes

  2019cites this paper
• Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication

  2019cites this paper
• 17(S),18(R)‐epoxyeicosatetraenoic acid generated by cytochrome P450 BM‐3 from Bacillus megaterium inhibits the development of contact hypersensitivity via G‐protein‐coupled receptor 40‐mediated neutrophil suppression

  2019cites this paper
• Gynura divaricata ameliorates hepatic insulin resistance by modulating insulin signalling, maintaining glycolipid homeostasis and reducing inflammation in type 2 diabetic mice.

  2019cites this paper
• Palmitic Acid Reduces the Autophagic Flux and Insulin Sensitivity Through the Activation of the Free Fatty Acid Receptor 1 (FFAR1) in the Hypothalamic Neuronal Cell Line N43/5

  2019cites this paper
• High Carbohydrate High Fat Diet Induced Hepatic Steatosis and Dyslipidemia Were Ameliorated by Psidium guajava Leaf Powder Supplementation in Rats

  2019cites this paper
• Pioglitazone Ameliorates Atorvastatin-Induced Islet Cell Dysfunction through Activation of FFA1 in INS-1 Cells

  2019cites this paper
• The role of Npas4 and Rgs2 in the regulation of pancreatic β-cell function

  2019cites this paper
• Title GPR 40 / FFAR 1 deficient mice increase noradrenaline levels inthe brain and exhibit abnormal behavior

  2019cites this paper
• Oleic acid antagonizes the action of high fructose high fat diet on insulin secretion and adipose tissue β-arrestin signaling

  2019cites this paper
• Free fatty acid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

  2019cites this paper
• Current status of GPR40/FFAR1 modulators in medicinal chemistry (2016–2019): a patent review

  2019cites this paper
• Effects of Dietary Fatty Acids in Pancreatic Beta Cell Metabolism, Implications in Homeostasis

  2018cites this paper
• 20-HETE promotes glucose-stimulated insulin secretion in an autocrine manner through FFAR1

  2018cites this paper
• Considerations and guidelines for mouse metabolic phenotyping in diabetes research

  2018cites this paper
• Developmental molecular biology of the pancreas

  2018cites this paper
• Fasiglifam (TAK-875), a G Protein-Coupled Receptor 40 (GPR40) Agonist, May Induce Hepatotoxicity through Reactive Oxygen Species Generation in a GPR40-Dependent Manner

  2018cites this paper
• The role of the liver in glucose and lipid metabolism in obesity

  2018cites this paper
• The Good , the Bad , and the Ugly – role of the pancreas , endothelium , and adipose tissue axis in the management of pancreatic β-cell failure in obesity-related type 2 diabetes

  2018cites this paper
• Palmitic Acid Hydroxystearic Acids Activate GPR40, Which Is Involved in Their Beneficial Effects on Glucose Homeostasis.

  2018cites this paper
• Therapeutic potential of ectopic olfactory and taste receptors

  2018cites this paper
• Chemoreceptors in the Gut.

  2018cites this paper
• Role of GPR40 in pathogenesis and treatment of Alzheimer's disease and type 2 diabetic dementia

  2018cites this paper
• Fatty Acid-Induced Lipotoxicity in Pancreatic Beta-Cells During Development of Type 2 Diabetes

  2018cites this paper
• Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1

  2018cites this paper
• Free fatty acid receptor 1 as a novel therapeutic target for type 2 diabetes mellitus-current status.

  2018cites this paper