Striking a gut-liver balance for the antidiabetic effects of metformin.

[1]  H. Reich,et al.  Metformin triggers a kidney GDF15-dependent area postrema axis to regulate food intake and body weight. , 2023, Cell metabolism.

[2]  S. Q. Brunetto,et al.  Metformin acts in the gut and induces gut-liver crosstalk , 2023, Proceedings of the National Academy of Sciences of the United States of America.

[3]  D. Huglo,et al.  Oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of sodium-glucose co-transporter 1 in enterocytes , 2023, iScience.

[4]  W. Wahli,et al.  A positive feedback loop between AMPK and GDF15 promotes metformin antidiabetic effects. , 2022, Pharmacological research.

[5]  A. Coll,et al.  Metformin and GDF15: where are we now? , 2022, Nature reviews. Endocrinology.

[6]  C. Rayner,et al.  Normal and disordered gastric emptying in diabetes: recent insights into (patho)physiology, management and impact on glycaemic control , 2022, Diabetologia.

[7]  R. Thring,et al.  Tauroursodeoxycholic acid functions as a critical effector mediating insulin sensitization of metformin in obese mice , 2022, Redox biology.

[8]  W. Wahli,et al.  Knocking on GDF15’s door for the treatment of type 2 diabetes mellitus , 2022, Trends in Endocrinology & Metabolism.

[9]  J. Hirst,et al.  Structural Basis of Mammalian Respiratory Complex I Inhibition by Medicinal Biguanides , 2022, bioRxiv.

[10]  T. Lam,et al.  Metabolic regulation by the intestinal metformin-AMPK axis , 2022, Nature Communications.

[11]  M. Hollenberg,et al.  Metformin: Is it a drug for all reasons and diseases? , 2022, Metabolism: clinical and experimental.

[12]  Shao-Hua Yang,et al.  Let-7 underlies metformin-induced inhibition of hepatic glucose production , 2022, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Y. Bao,et al.  Low-dose metformin targets the lysosomal AMPK pathway through PEN2 , 2022, Nature.

[14]  R. Seeley,et al.  The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance , 2022, bioRxiv.

[15]  Ki Baek Lee,et al.  Body weight regulation via MT1-MMP-mediated cleavage of GFRAL , 2022, Nature Metabolism.

[16]  A. Kautzky-Willer,et al.  Deciphering metformin action in obese mice: A critical re-evaluation of established protocols. , 2021, Metabolism: clinical and experimental.

[17]  M. Nogami,et al.  Metformin action in the gut―insight provided by [18F]FDG PET imaging , 2021, Diabetology International.

[18]  Scott C. Thomas,et al.  The Gut Microbiome, Metformin, and Aging. , 2021, Annual review of pharmacology and toxicology.

[19]  J. Holst,et al.  Metformin Stimulates Intestinal Glycolysis and Lactate Release: A single‐Dose Study of Metformin in Patients With Intrahepatic Portosystemic Stent , 2021, Clinical pharmacology and therapeutics.

[20]  R. M. Gomes,et al.  Metformin Improves Autonomic Nervous System Imbalance and Metabolic Dysfunction in Monosodium L-Glutamate-Treated Rats , 2021, Frontiers in Endocrinology.

[21]  S. Stoker,et al.  Metformin’s Therapeutic Efficacy in the Treatment of Diabetes Does Not Involve Inhibition of Mitochondrial Glycerol Phosphate Dehydrogenase , 2021, Diabetes.

[22]  S. O’Rahilly,et al.  Inhibition of mitochondrial function by metformin increases glucose uptake, glycolysis and GDF-15 release from intestinal cells , 2021, Scientific Reports.

[23]  A. Riggs,et al.  Intestinal AMPK modulation of microbiota mediates crosstalk with brown fat to control thermogenesis , 2021, Nature Communications.

[24]  Y. Xin,et al.  Role of the gut microbiota in type 2 diabetes and related diseases. , 2021, Metabolism: clinical and experimental.

[25]  R. Seeley,et al.  Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise , 2020, Nature Communications.

[26]  Ling He.  Metformin and Systemic Metabolism. , 2020, Trends in pharmacological sciences.

[27]  G. Shulman,et al.  Cellular and Molecular Mechanisms of Metformin Action , 2020, Endocrine reviews.

[28]  T. Murakami,et al.  Enhanced Release of Glucose Into the Intraluminal Space of the Intestine Associated With Metformin Treatment as Revealed by [18F]Fluorodeoxyglucose PET-MRI , 2020, Diabetes Care.

[29]  B. Viollet,et al.  Metformin lowers glucose 6-phosphate in hepatocytes by activation of glycolysis downstream of glucose phosphorylation , 2020, The Journal of Biological Chemistry.

[30]  S. O’Rahilly,et al.  GDF15 mediates the effects of metformin on body weight and energy balance , 2019, Nature.

[31]  Amogelang R. Raphenya,et al.  Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss , 2019, Nature Metabolism.

[32]  N. Jackson,et al.  Metformin increases fasting glucose clearance and endogenous glucose production in non-diabetic individuals , 2019, Diabetologia.

[33]  O. Lutz,et al.  Pharmacology of metformin - An update. , 2019, European journal of pharmacology.

[34]  F. Wondisford,et al.  Metformin Improves Mitochondrial Respiratory Activity through Activation of AMPK , 2019, Cell reports.

[35]  H. McNulty,et al.  Hyperglycemia and metformin use are associated with B-vitamin deficiency and cognitive dysfunction in older adults. , 2019, The Journal of clinical endocrinology and metabolism.

[36]  B. Viollet,et al.  Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus , 2019, Nature Reviews Endocrinology.

[37]  M. Horowitz,et al.  Mechanism of glucose‐lowering by metformin in type 2 diabetes: Role of bile acids , 2019, Diabetes, obesity & metabolism.

[38]  M. Horowitz,et al.  Gastric Emptying in Patients With Well-Controlled Type 2 Diabetes Compared With Young and Older Control Subjects Without Diabetes. , 2019, The Journal of clinical endocrinology and metabolism.

[39]  L. Gormsen,et al.  Metformin increases endogenous glucose production in non-diabetic individuals and individuals with recent-onset type 2 diabetes , 2019, Diabetologia.

[40]  J. Holst,et al.  Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes. , 2018, JCI insight.

[41]  M. Horowitz,et al.  Comparative effects of proximal and distal small intestinal administration of metformin on plasma glucose and glucagon‐like peptide‐1, and gastric emptying after oral glucose, in type 2 diabetes , 2018, Diabetes, obesity & metabolism.

[42]  William H. Bisson,et al.  Gut microbiota and intestinal FXR mediate the clinical benefits of metformin , 2018, Nature Medicine.

[43]  P. Groop,et al.  Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity , 2018, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[44]  M. Horowitz,et al.  Role of Intestinal Bitter Sensing in Enteroendocrine Hormone Secretion and Metabolic Control , 2018, Front. Endocrinol..

[45]  Gina M. Butrico,et al.  Metformin Inhibits Gluconeogenesis by a Redox-Dependent Mechanism In Vivo , 2018, Nature Medicine.

[46]  M. Nauck,et al.  Incretin hormones: Their role in health and disease , 2018, Diabetes, obesity & metabolism.

[47]  T. Z. Waise,et al.  Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway. , 2018, Cell metabolism.

[48]  J. Holst,et al.  Single‐Dose Metformin Enhances Bile Acid‐Induced Glucagon‐Like Peptide‐1 Secretion in Patients With Type 2 Diabetes , 2017, The Journal of clinical endocrinology and metabolism.

[49]  Jie Tang,et al.  Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15 , 2017, Nature.

[50]  P. Iozzo,et al.  Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes: Results from a randomized clinical trial. , 2017, Diabetes research and clinical practice.

[51]  Søren B. Padkjær,et al.  GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand , 2017, Nature Medicine.

[52]  T. Cash-Mason,et al.  GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates , 2017, Nature Medicine.

[53]  P. Emmerson,et al.  The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL , 2017, Nature Medicine.

[54]  Jinyang Wang,et al.  Metformin ameliorates skeletal muscle insulin resistance by inhibiting miR-21 expression in a high-fat dietary rat model , 2017, Oncotarget.

[55]  R. Shaw,et al.  AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance. , 2017, Molecular cell.

[56]  David Torrents,et al.  Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug , 2017, Nature Medicine.

[57]  M. D. de Angelis,et al.  Metformin causes a futile intestinal–hepatic cycle which increases energy expenditure and slows down development of a type 2 diabetes-like state , 2017, Molecular metabolism.

[58]  H. Gerstein,et al.  Growth Differentiation Factor 15 as a Novel Biomarker for Metformin , 2016, Diabetes Care.

[59]  S. Jakobsen,et al.  In Vivo Imaging of Human 11C-Metformin in Peripheral Organs: Dosimetry, Biodistribution, and Kinetic Analyses , 2016, The Journal of Nuclear Medicine.

[60]  Jacobo de la Cuesta-Zuluaga,et al.  Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid–Producing Microbiota in the Gut , 2016, Diabetes Care.

[61]  Chen-Song Zhang,et al.  Metformin Activates AMPK through the Lysosomal Pathway. , 2016, Cell metabolism.

[62]  T. Vilsbøll,et al.  Involvement of glucagon‐like peptide‐1 in the glucose‐lowering effect of metformin , 2016, Diabetes, obesity & metabolism.

[63]  P. Bork,et al.  Human gut microbes impact host serum metabolome and insulin sensitivity , 2016, Nature.

[64]  R. DeFronzo,et al.  Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials , 2016, Diabetologia.

[65]  F. Holleman,et al.  Metformin-related colonic glucose uptake; potential role for increasing glucose disposal?--A retrospective analysis of (18)F-FDG uptake in the colon on PET-CT. , 2016, Diabetes research and clinical practice.

[66]  S. Jakobsen,et al.  [11C]-Labeled Metformin Distribution in the Liver and Small Intestine Using Dynamic Positron Emission Tomography in Mice Demonstrates Tissue-Specific Transporter Dependency , 2016, Diabetes.

[67]  G. A. Fleming,et al.  Metformin-associated lactic acidosis: Current perspectives on causes and risk. , 2016, Metabolism: clinical and experimental.

[68]  C. Bailey,et al.  Metformin and the gastrointestinal tract , 2016, Diabetologia.

[69]  Ruisheng Song.  Mechanism of Metformin: A Tale of Two Sites , 2016, Diabetes Care.

[70]  V. Víctor,et al.  Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance. , 2015, European journal of endocrinology.

[71]  Jens Roat Kultima,et al.  Disentangling the effects of type 2 diabetes and metformin on the human gut microbiota , 2016 .

[72]  R. DeFronzo,et al.  The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies , 2015, Diabetes Care.

[73]  G. Rutter,et al.  Metformin activates a duodenal Ampk–dependent pathway to lower hepatic glucose production in rats , 2015, Nature Medicine.

[74]  F. Wondisford,et al.  Metformin action: concentrations matter. , 2015, Cell metabolism.

[75]  C. Palmer,et al.  Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study , 2014, Diabetes.

[76]  R. Cole,et al.  Low Concentrations of Metformin Suppress Glucose Production in Hepatocytes through AMP-activated Protein Kinase (AMPK)*♦ , 2014, The Journal of Biological Chemistry.

[77]  Michael J. MacDonald,et al.  Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase , 2014, Nature.

[78]  P. Schjerling,et al.  Two weeks of metformin treatment induces AMPK-dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle. , 2014, American journal of physiology. Endocrinology and metabolism.

[79]  Céline Gheeraert,et al.  Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk. , 2014, The Journal of clinical investigation.

[80]  J. Dyck,et al.  Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin–sensitizing effects of metformin , 2013, Nature Medicine.

[81]  O. Shirihai,et al.  Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. , 2013, Cell metabolism.

[82]  B. Viollet,et al.  Biguanides suppress hepatic glucagon signaling by decreasing production of cyclic AMP , 2016 .

[83]  S. Larsen,et al.  Metformin-treated patients with type 2 diabetes have normal mitochondrial complex I respiration , 2012, Diabetologia.

[84]  M. White,et al.  Insulin signaling meets mitochondria in metabolism , 2010, Trends in Endocrinology & Metabolism.

[85]  B. Viollet,et al.  Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. , 2010, The Journal of clinical investigation.

[86]  R. DeFronzo,et al.  Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes , 2009, Diabetes Care.

[87]  J. Auwerx,et al.  TGR5-mediated bile acid sensing controls glucose homeostasis. , 2009, Cell metabolism.

[88]  F. Wondisford,et al.  Metformin and Insulin Suppress Hepatic Gluconeogenesis through Phosphorylation of CREB Binding Protein , 2009, Cell.

[89]  C. Bailey,et al.  Metformin and the intestine , 2008, Diabetologia.

[90]  In-kyu Lee,et al.  Metformin Inhibits Hepatic Gluconeogenesis Through AMP-Activated Protein Kinase–Dependent Regulation of the Orphan Nuclear Receptor SHP , 2008, Diabetes.

[91]  J. Ferrières,et al.  Metabolic Endotoxemia Initiates Obesity and Insulin Resistance , 2007, Diabetes.

[92]  R. DePinho,et al.  The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin , 2005, Science.

[93]  Olle Ljunqvist,et al.  Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. , 2002, Diabetes.

[94]  Margaret S. Wu,et al.  Role of AMP-activated protein kinase in mechanism of metformin action. , 2001, The Journal of clinical investigation.

[95]  A. Spungen,et al.  Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. , 2000, Diabetes care.

[96]  G Dailey,et al.  Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. , 1995, The New England journal of medicine.

[97]  C. Catalano,et al.  The Effect of Intravenous Metformin on Glucose Metabolism During Hyperglycaemia in Type 2 Diabetes , 1992, Diabetic medicine : a journal of the British Diabetic Association.