Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic Impact for Metabolic Disease

[1]  Jeffrey R. Chabot,et al.  A Long-Acting FGF21 Molecule, PF-05231023, Decreases Body Weight and Improves Lipid Profile in Non-human Primates and Type 2 Diabetic Subjects. , 2016, Cell metabolism.

[2]  Sean M. Hartig,et al.  Pharmacological Activation of Thyroid Hormone Receptors Elicits a Functional Conversion of White to Brown Fat. , 2015, Cell reports.

[3]  Y. Wan,et al.  A Liver-Bone Endocrine Relay by IGFBP1 Promotes Osteoclastogenesis and Mediates FGF21-Induced Bone Resorption. , 2015, Cell metabolism.

[4]  R. Gimeno,et al.  Discrete Aspects of FGF21 In Vivo Pharmacology Do Not Require UCP1. , 2015, Cell reports.

[5]  R. DiMarchi,et al.  Effect of targeted estrogen delivery using glucagon-like peptide-1 on insulin secretion, insulin sensitivity and glucose homeostasis , 2015, Scientific Reports.

[6]  M. Véniant,et al.  Pharmacologic Effects of FGF21 Are Independent of the "Browning" of White Adipose Tissue. , 2015, Cell metabolism.

[7]  D. Diamond,et al.  How statistical deception created the appearance that statins are safe and effective in primary and secondary prevention of cardiovascular disease , 2015, Expert review of clinical pharmacology.

[8]  M. Tschöp,et al.  GLP-1–oestrogen attenuates hyperphagia and protects from beta cell failure in diabetes-prone New Zealand obese (NZO) mice , 2014, Diabetologia.

[9]  R. Seeley,et al.  A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents , 2014, Nature Medicine.

[10]  W. Huber,et al.  Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 , 2014, Genome Biology.

[11]  H. Moch,et al.  Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes nonalcoholic steatohepatitis and liver cancer via cross-talk with hepatocytes. , 2014, Cancer cell.

[12]  B. Singh,et al.  Thyroid hormone regulation of hepatic lipid and carbohydrate metabolism , 2014, Trends in Endocrinology & Metabolism.

[13]  P. Ladenson,et al.  Eprotirome in patients with familial hypercholesterolaemia (the AKKA trial): a randomised, double-blind, placebo-controlled phase 3 study. , 2014, The lancet. Diabetes & endocrinology.

[14]  S. Fleury,et al.  TRα protects against atherosclerosis in male mice: identification of a novel anti-inflammatory property for TRα in mice. , 2014, Endocrinology.

[15]  S. So,et al.  Discovery of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile (MGL-3196), a Highly Selective Thyroid Hormone Receptor β agonist in clinical trials for the treatment of dyslipidemia. , 2014, Journal of medicinal chemistry.

[16]  G. Brent,et al.  Thyroid hormone regulation of metabolism. , 2014, Physiological reviews.

[17]  J. Flier,et al.  Fibroblast growth factor 21 and thyroid hormone show mutual regulatory dependency but have independent actions in vivo. , 2014, Endocrinology.

[18]  J. Allard,et al.  Clinical approaches to non-alcoholic fatty liver disease. , 2014, World journal of gastroenterology.

[19]  J. Samarut,et al.  The targeted inactivation of TRβ gene in thyroid follicular cells suggests a new mechanism of regulation of thyroid hormone production. , 2014, Endocrinology.

[20]  A. Adams,et al.  Inventing new medicines: The FGF21 story☆ , 2013, Molecular metabolism.

[21]  G. Shulman,et al.  Reversal of hypertriglyceridemia, fatty liver disease, and insulin resistance by a liver-targeted mitochondrial uncoupler. , 2013, Cell metabolism.

[22]  Bin Yang,et al.  Unimolecular Dual Incretins Maximize Metabolic Benefits in Rodents, Monkeys, and Humans , 2013, Science Translational Medicine.

[23]  J. Tardif,et al.  Lipid lowering in healthy volunteers treated with multiple doses of MGL-3196, a liver-targeted thyroid hormone receptor-β agonist. , 2013, Atherosclerosis.

[24]  H. Fu,et al.  The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. , 2013, Cell metabolism.

[25]  F. Villarroya,et al.  Fibroblast growth factor 21 protects against cardiac hypertrophy in mice , 2013, Nature Communications.

[26]  S. Woods,et al.  Fibroblast Growth Factor 21 Mediates Specific Glucagon Actions , 2013, Diabetes.

[27]  Bin Yang,et al.  Targeted estrogen delivery reverses the metabolic syndrome , 2012, Nature Medicine.

[28]  W. Hsueh,et al.  Thyroid hormone receptor agonists reduce serum cholesterol independent of the LDL receptor. , 2012, Endocrinology.

[29]  B. Bay,et al.  Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy. , 2012, The Journal of clinical investigation.

[30]  S. Kliewer,et al.  Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γ , 2012, Proceedings of the National Academy of Sciences.

[31]  Peter Libby,et al.  Effect of two intensive statin regimens on progression of coronary disease. , 2011, The New England journal of medicine.

[32]  B. Spiegelman,et al.  Integrated regulation of hepatic metabolism by fibroblast growth factor 21 (FGF21) in vivo. , 2011, Endocrinology.

[33]  M. Tschöp,et al.  The metabolic actions of glucagon revisited , 2010, Nature Reviews Endocrinology.

[34]  P. Ladenson,et al.  Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins: a pilot prospective, randomized, controlled study. , 2010, The Journal of clinical endocrinology and metabolism.

[35]  S. Woods,et al.  A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. , 2009, Nature chemical biology.

[36]  M. Konishi,et al.  Fibroblast growth factor 21 regulates lipolysis in white adipose tissue but is not required for ketogenesis and triglyceride clearance in liver. , 2009, Endocrinology.

[37]  J. Baxter,et al.  Thyroid hormone mimetics: potential applications in atherosclerosis, obesity and type 2 diabetes , 2009, Nature Reviews Drug Discovery.

[38]  D. Bauer,et al.  Meta-analysis: Subclinical Thyroid Dysfunction and the Risk for Coronary Heart Disease and Mortality , 2008, Annals of Internal Medicine.

[39]  J. E. Silva,et al.  Thermogenic mechanisms and their hormonal regulation. , 2006, Physiological reviews.

[40]  D. Kelly,et al.  PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. , 2006, The Journal of clinical investigation.

[41]  Christoph Handschin,et al.  Metabolic control through the PGC-1 family of transcription coactivators. , 2005, Cell metabolism.

[42]  Waljit S Dhillo,et al.  Triiodothyronine stimulates food intake via the hypothalamic ventromedial nucleus independent of changes in energy expenditure. , 2004, Endocrinology.

[43]  Johan Malm,et al.  Selective thyroid hormone receptor-β activation: A strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[44]  Marc Montminy,et al.  CREB regulates hepatic gluconeogenesis through the coactivator PGC-1 , 2001, Nature.

[45]  R J Fletterick,et al.  Hormone selectivity in thyroid hormone receptors. , 2001, Molecular endocrinology.

[46]  C. Kellendonk,et al.  Hepatocyte‐specific expression of Cre recombinase , 2000, Genesis.

[47]  B. Cannon,et al.  Apparent thermogenic effect of injected glucagon is not due to a direct effect on brown fat cells. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[48]  R. Burcelin,et al.  Cloning and sequence analysis of the murine glucagon receptor-encoding gene. , 1995, Gene.

[49]  A. Levine,et al.  Glucagon in physiological concentrations stimulates brown fat thermogenesis in vivo. , 1991, The American journal of physiology.

[50]  M. Obregon,et al.  Effects of maternal hypothyroidism on the weight and thyroid hormone content of rat embryonic tissues, before and after onset of fetal thyroid function. , 1985, Endocrinology.

[51]  M. Reitman,et al.  Effect of Glucagon on the Metabolism of Lipids and on Urea Formation by the Perfused Rat Liver , 1966, Diabetes.

[52]  A. Bianco,et al.  Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue. , 1987, The Journal of clinical investigation.