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Glucose-Dependent Insulinotropic Polypeptide Receptor Therapies For The Treatment Of Obesity, Do Agonists = Antagonists?

Killion EA, Lu SC, Fort M, Yamada Y, Véniant MM, Lloyd DJ.

Endocr Rev. 2019 Sep 12. pii: bnz002. doi: 10.1210/endrev/bnz002. [Epub ahead of print]


Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models.

Killion EA, Wang J, Yie J, Shi SD, Bates D, Min X, Komorowski R, Hager T, Deng L, Atangan L, Lu SC, Kurzeja RJM, Sivits G, Lin J, Chen Q, Wang Z, Thibault SA, Abbott CM, Meng T, Clavette B, Murawsky CM, Foltz IN, Rottman JB, Hale C, Véniant MM, Lloyd DJ.

Sci Transl Med. 2018 Dec 19;10(472). pii: eaat3392. doi: 10.1126/scitranslmed.aat3392.


Controlled aqueous polymerization of acrylamides and acrylates and "in situ" depolymerization in the presence of dissolved CO2.

Lloyd DJ, Nikolaou V, Collins J, Waldron C, Anastasaki A, Bassett SP, Howdle SM, Blanazs A, Wilson P, Kempe K, Haddleton DM.

Chem Commun (Camb). 2016 May 5;52(39):6533-6. doi: 10.1039/c6cc03027k.


Haploinsufficiency of the Insulin Receptor in the Presence of a Splice-Site Mutation in Ppp2r2a Results in a Novel Digenic Mouse Model of Type 2 Diabetes.

Goldsworthy M, Bai Y, Li CM, Ge H, Lamas E, Hilton H, Esapa CT, Baker D, Baron W, Juan T, Véniant MM, Lloyd DJ, Cox RD.

Diabetes. 2016 May;65(5):1434-46. doi: 10.2337/db15-1276. Epub 2016 Feb 11.


Discovery and Structure-Guided Optimization of Diarylmethanesulfonamide Disrupters of Glucokinase-Glucokinase Regulatory Protein (GK-GKRP) Binding: Strategic Use of a N → S (nN → σ*S-X) Interaction for Conformational Constraint.

Pennington LD, Bartberger MD, Croghan MD, Andrews KL, Ashton KS, Bourbeau MP, Chen J, Chmait S, Cupples R, Fotsch C, Helmering J, Hong FT, Hungate RW, Jordan SR, Kong K, Liu L, Michelsen K, Moyer C, Nishimura N, Norman MH, Reichelt A, Siegmund AC, Sivits G, Tadesse S, Tegley CM, Van G, Yang KC, Yao G, Zhang J, Lloyd DJ, Hale C, St Jean DJ Jr.

J Med Chem. 2015 Dec 24;58(24):9663-79. doi: 10.1021/acs.jmedchem.5b01367. Epub 2015 Dec 1.


Pharmacologic Effects of FGF21 Are Independent of the "Browning" of White Adipose Tissue.

Véniant MM, Sivits G, Helmering J, Komorowski R, Lee J, Fan W, Moyer C, Lloyd DJ.

Cell Metab. 2015 May 5;21(5):731-8. doi: 10.1016/j.cmet.2015.04.019.


Small Molecule Disruptors of the Glucokinase-Glucokinase Regulatory Protein Interaction: 5. A Novel Aryl Sulfone Series, Optimization Through Conformational Analysis.

Tamayo NA, Norman MH, Bartberger MD, Hong FT, Bo Y, Liu L, Nishimura N, Yang KC, Tadesse S, Fotsch C, Chen J, Chmait S, Cupples R, Hale C, Jordan SR, Lloyd DJ, Sivits G, Van G, St Jean DJ Jr.

J Med Chem. 2015 Jun 11;58(11):4462-82. doi: 10.1021/jm5018175. Epub 2015 Jun 1.


A mutation in Ampd2 is associated with nephrotic syndrome and hypercholesterolemia in mice.

Helmering J, Juan T, Li CM, Chhoa M, Baron W, Gyuris T, Richards WG, Turk JR, Lawrence J, Cosgrove PA, Busby J, Kim KW, Kaufman SA, Cummings C, Carlson G, Véniant MM, Lloyd DJ.

Lipids Health Dis. 2014 Oct 31;13:167. doi: 10.1186/1476-511X-13-167.


A gain-of-function mutation in adenylate cyclase 3 protects mice from diet-induced obesity.

Pitman JL, Wheeler MC, Lloyd DJ, Walker JR, Glynne RJ, Gekakis N.

PLoS One. 2014 Oct 16;9(10):e110226. doi: 10.1371/journal.pone.0110226. eCollection 2014.


Molecular targeting of the GK-GKRP pathway in diabetes.

Hale C, Lloyd DJ, Pellacani A, Véniant MM.

Expert Opin Ther Targets. 2015 Jan;19(1):129-39. doi: 10.1517/14728222.2014.965681. Epub 2014 Oct 17. Review.


Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 4. Exploration of a novel binding pocket.

Hong FT, Norman MH, Ashton KS, Bartberger MD, Chen J, Chmait S, Cupples R, Fotsch C, Jordan SR, Lloyd DJ, Sivits G, Tadesse S, Hale C, St Jean DJ Jr.

J Med Chem. 2014 Jul 24;57(14):5949-64. doi: 10.1021/jm5001979. Epub 2014 Jul 8.


Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 3. Structure-activity relationships within the aryl carbinol region of the N-arylsulfonamido-N'-arylpiperazine series.

Nishimura N, Norman MH, Liu L, Yang KC, Ashton KS, Bartberger MD, Chmait S, Chen J, Cupples R, Fotsch C, Helmering J, Jordan SR, Kunz RK, Pennington LD, Poon SF, Siegmund A, Sivits G, Lloyd DJ, Hale C, St Jean DJ Jr.

J Med Chem. 2014 Apr 10;57(7):3094-116. doi: 10.1021/jm5000497. Epub 2014 Mar 31.


The effect of the G1-S transition checkpoint on an age structured cell cycle model.

Chaffey GS, Lloyd DJ, Skeldon AC, Kirkby NF.

PLoS One. 2014 Jan 9;9(1):e83477. doi: 10.1371/journal.pone.0083477. eCollection 2014.


Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 2. Leveraging structure-based drug design to identify analogues with improved pharmacokinetic profiles.

St Jean DJ Jr, Ashton KS, Bartberger MD, Chen J, Chmait S, Cupples R, Galbreath E, Helmering J, Hong FT, Jordan SR, Liu L, Kunz RK, Michelsen K, Nishimura N, Pennington LD, Poon SF, Reid D, Sivits G, Stec MM, Tadesse S, Tamayo N, Van G, Yang KC, Zhang J, Norman MH, Fotsch C, Lloyd DJ, Hale C.

J Med Chem. 2014 Jan 23;57(2):325-38. doi: 10.1021/jm4016747. Epub 2014 Jan 9.


Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 1. Discovery of a novel tool compound for in vivo proof-of-concept.

Ashton KS, Andrews KL, Bryan MC, Chen J, Chen K, Chen M, Chmait S, Croghan M, Cupples R, Fotsch C, Helmering J, Jordan SR, Kurzeja RJ, Michelsen K, Pennington LD, Poon SF, Sivits G, Van G, Vonderfecht SL, Wahl RC, Zhang J, Lloyd DJ, Hale C, St Jean DJ Jr.

J Med Chem. 2014 Jan 23;57(2):309-24. doi: 10.1021/jm4016735. Epub 2014 Jan 9. Erratum in: J Med Chem. 2014 Mar 27;57(6):2820. Bryan, Marion C [corrected to Bryan, Marian C].


Participatory development and analysis of a fuzzy cognitive map of the establishment of a bio-based economy in the Humber region.

Penn AS, Knight CJ, Lloyd DJ, Avitabile D, Kok K, Schiller F, Woodward A, Druckman A, Basson L.

PLoS One. 2013 Nov 7;8(11):e78319. doi: 10.1371/journal.pone.0078319. eCollection 2013.


Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors.

Lloyd DJ, St Jean DJ Jr, Kurzeja RJ, Wahl RC, Michelsen K, Cupples R, Chen M, Wu J, Sivits G, Helmering J, Komorowski R, Ashton KS, Pennington LD, Fotsch C, Vazir M, Chen K, Chmait S, Zhang J, Liu L, Norman MH, Andrews KL, Bartberger MD, Van G, Galbreath EJ, Vonderfecht SL, Wang M, Jordan SR, Véniant MM, Hale C.

Nature. 2013 Dec 19;504(7480):437-40. doi: 10.1038/nature12724. Epub 2013 Nov 13.


FGF21 promotes metabolic homeostasis via white adipose and leptin in mice.

Véniant MM, Hale C, Helmering J, Chen MM, Stanislaus S, Busby J, Vonderfecht S, Xu J, Lloyd DJ.

PLoS One. 2012;7(7):e40164. doi: 10.1371/journal.pone.0040164. Epub 2012 Jul 6.


Modelling and detecting tumour oxygenation levels.

Skeldon AC, Chaffey G, Lloyd DJ, Mohan V, Bradley DA, Nisbet A.

PLoS One. 2012;7(6):e38597. doi: 10.1371/journal.pone.0038597. Epub 2012 Jun 28.


A volumetric method for quantifying atherosclerosis in mice by using microCT: comparison to en face.

Lloyd DJ, Helmering J, Kaufman SA, Turk J, Silva M, Vasquez S, Weinstein D, Johnston B, Hale C, Véniant MM.

PLoS One. 2011 Apr 18;6(4):e18800. doi: 10.1371/journal.pone.0018800.


Pharmacological targeting of glucagon and glucagon-like peptide 1 receptors has different effects on energy state and glucose homeostasis in diet-induced obese mice.

Gu W, Lloyd DJ, Chinookswong N, Komorowski R, Sivits G Jr, Graham M, Winters KA, Yan H, Boros LG, Lindberg RA, Véniant MM.

J Pharmacol Exp Ther. 2011 Jul;338(1):70-81. doi: 10.1124/jpet.111.179986. Epub 2011 Apr 6.


Spontaneous emergence of long-range shape symmetry.

Shiozawa H, Skeldon AC, Lloyd DJ, Stolojan V, Cox DC, Silva SR.

Nano Lett. 2011 Jan 12;11(1):160-3. doi: 10.1021/nl1032793. Epub 2010 Dec 13.


Risk of skin cancer after neonatal phototherapy: retrospective cohort study.

Brewster DH, Tucker JS, Fleming M, Morris C, Stockton DL, Lloyd DJ, Bhattacharya S, Chalmers JW.

Arch Dis Child. 2010 Oct;95(10):826-31. doi: 10.1136/adc.2009.179275. Epub 2010 Jun 23.


A point mutation in Sec61alpha1 leads to diabetes and hepatosteatosis in mice.

Lloyd DJ, Wheeler MC, Gekakis N.

Diabetes. 2010 Feb;59(2):460-70. doi: 10.2337/db08-1362. Epub 2009 Nov 23.


Antidiabetic effects of 11beta-HSD1 inhibition in a mouse model of combined diabetes, dyslipidaemia and atherosclerosis.

Lloyd DJ, Helmering J, Cordover D, Bowsman M, Chen M, Hale C, Fordstrom P, Zhou M, Wang M, Kaufman SA, Véniant MM.

Diabetes Obes Metab. 2009 Jul;11(7):688-99. doi: 10.1111/j.1463-1326.2009.01034.x.


New variants in the Enpp1 and Ptpn6 genes cause low BMD, crystal-related arthropathy, and vascular calcification.

Babij P, Roudier M, Graves T, Han CY, Chhoa M, Li CM, Juan T, Morony S, Grisanti M, Li X, Yu L, Dwyer D, Lloyd DJ, Bass MB, Richards WG, Ebeling C, Amato J, Carlson G.

J Bone Miner Res. 2009 Sep;24(9):1552-64. doi: 10.1359/jbmr.090417.


Loss-of-function mutation in myostatin reduces tumor necrosis factor alpha production and protects liver against obesity-induced insulin resistance.

Wilkes JJ, Lloyd DJ, Gekakis N.

Diabetes. 2009 May;58(5):1133-43. doi: 10.2337/db08-0245. Epub 2009 Feb 10.


Pancreatic islet expression profiling in diabetes-prone C57BLKS/J mice reveals transcriptional differences contributed by DBA loci, including Plagl1 and Nnt.

Anderson AA, Helmering J, Juan T, Li CM, McCormick J, Graham M, Baker DM, Damore MA, Véniant MM, Lloyd DJ.

Pathogenetics. 2009 Jan 22;2(1):1. doi: 10.1186/1755-8417-2-1.


Identification of three loci affecting HDL-cholesterol levels in a screen for chemically induced recessive mutations in mice.

Juan T, Véniant MM, Helmering J, Babij P, Baker DM, Damore MA, Bass MB, Gyuris T, Chhoa M, Li CM, Ebeling C, Amato J, Carlson GA, Lloyd DJ.

J Lipid Res. 2009 Mar;50(3):534-45. doi: 10.1194/jlr.M800471-JLR200. Epub 2008 Oct 29.


Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice.

Xu J, Lloyd DJ, Hale C, Stanislaus S, Chen M, Sivits G, Vonderfecht S, Hecht R, Li YS, Lindberg RA, Chen JL, Jung DY, Zhang Z, Ko HJ, Kim JK, Véniant MM.

Diabetes. 2009 Jan;58(1):250-9. doi: 10.2337/db08-0392. Epub 2008 Oct 7.


Generation and characterization of two novel mouse models exhibiting the phenotypes of the metabolic syndrome: Apob48-/-Lepob/ob mice devoid of ApoE or Ldlr.

Lloyd DJ, McCormick J, Helmering J, Kim KW, Wang M, Fordstrom P, Kaufman SA, Lindberg RA, Véniant MM.

Am J Physiol Endocrinol Metab. 2008 Mar;294(3):E496-505. Epub 2007 Dec 26.


SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton.

Haque F, Lloyd DJ, Smallwood DT, Dent CL, Shanahan CM, Fry AM, Trembath RC, Shackleton S.

Mol Cell Biol. 2006 May;26(10):3738-51.


Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice.

Lloyd DJ, Bohan S, Gekakis N.

Hum Mol Genet. 2006 Jun 1;15(11):1884-93. Epub 2006 Apr 27. Erratum in: Hum Mol Genet. 2008 Nov 1;17(21):3435.


Diabetes insipidus in mice with a mutation in aquaporin-2.

Lloyd DJ, Hall FW, Tarantino LM, Gekakis N.

PLoS Genet. 2005 Aug;1(2):e20. Epub 2005 Aug 19.


Characteristics of fetal anticonvulsant syndrome associated autistic disorder.

Rasalam AD, Hailey H, Williams JH, Moore SJ, Turnpenny PD, Lloyd DJ, Dean JC.

Dev Med Child Neurol. 2005 Aug;47(8):551-5.


Suboptimal care and perinatal mortality in ten European regions: methodology and evaluation of an international audit.

Richardus JH, Graafmans WC, Bergsjø P, Lloyd DJ, Bakketeig LS, Bannon EM, Borkent-Polet M, Davidson LL, Defoort P, Leitão AE, Langhoff-Roos J, Garcia AM, Papantoniou NE, Wennergren M, Amelink-Verburg MP, Verloove-Vanhorick SP, Mackenbach JP; EuroNatal Working Group.

J Matern Fetal Neonatal Med. 2003 Oct;14(4):267-76.


Donor exposure rate to transfusion ratio: a better discriminator of improvement in neonatal transfusion practice.

Ibojie J, Greiss M, Lloyd DJ, Urbaniak SJ.

Transfus Med. 2003 Oct;13(5):287-91.


Expression of kinase suppressor of Ras in the normal adult and embryonic mouse.

Giblett SM, Lloyd DJ, Light Y, Marais R, Pritchard CA.

Cell Growth Differ. 2002 Jul;13(7):307-13.


Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth.

Dean JC, Hailey H, Moore SJ, Lloyd DJ, Turnpenny PD, Little J.

J Med Genet. 2002 Apr;39(4):251-9.


A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies.

Lloyd DJ, Trembath RC, Shackleton S.

Hum Mol Genet. 2002 Apr 1;11(7):769-77.


Consent to autopsy for neonates.

McHaffie HE, Fowlie PW, Hume R, Laing IA, Lloyd DJ, Lyon AJ.

Arch Dis Child Fetal Neonatal Ed. 2001 Jul;85(1):F4-7.


Follow up care of bereaved parents after treatment withdrawal from newborns.

McHaffie HE, Laing IA, Lloyd DJ.

Arch Dis Child Fetal Neonatal Ed. 2001 Mar;84(2):F125-8.


Foveate vision in deep-sea teleosts: a comparison of primary visual and olfactory inputs.

Collin SP, Lloyd DJ, Wagner HJ.

Philos Trans R Soc Lond B Biol Sci. 2000 Sep 29;355(1401):1315-20. Review.


Lamin A/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy.

Vigouroux C, Magré J, Vantyghem MC, Bourut C, Lascols O, Shackleton S, Lloyd DJ, Guerci B, Padova G, Valensi P, Grimaldi A, Piquemal R, Touraine P, Trembath RC, Capeau J.

Diabetes. 2000 Nov;49(11):1958-62.


A clinical study of 57 children with fetal anticonvulsant syndromes.

Moore SJ, Turnpenny P, Quinn A, Glover S, Lloyd DJ, Montgomery T, Dean JC.

J Med Genet. 2000 Jul;37(7):489-97.


LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.

Shackleton S, Lloyd DJ, Jackson SN, Evans R, Niermeijer MF, Singh BM, Schmidt H, Brabant G, Kumar S, Durrington PN, Gregory S, O'Rahilly S, Trembath RC.

Nat Genet. 2000 Feb;24(2):153-6.


Investigation of corneal ablation efficiency using ultraviolet 213-nm solid state laser pulses.

Dair GT, Pelouch WS, van Saarloos PP, Lloyd DJ, Linares SM, Reinholz F.

Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2752-6.


Neonatal examination and screening trial (NEST): a randomised, controlled, switchback trial of alternative policies for low risk infants.

Glazener CM, Ramsay CR, Campbell MK, Booth P, Duffty P, Lloyd DJ, McDonald A, Reid JA.

BMJ. 1999 Mar 6;318(7184):627-31.


Small bowel injury in gastroschisis: relation to fetal presentation.

Bagley JS, Lloyd DJ, Gray ES, Youngson GG.

Br J Obstet Gynaecol. 1996 Oct;103(10):1047-8. No abstract available.


The accountability continuum--employers and the community.

Lloyd DJ.

Med Group Manage J. 1996 May-Jun;43(3):3, 70. No abstract available.


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