Research Topics
Genomes and Genes | Robert K SempleSummaryAffiliation: University of Cambridge Country: UK Publications
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Publications
Functional characterization of a novel insulin receptor mutation contributing to Rabson-Mendenhall syndromeA Tuthill
University of Cambridge Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge, UK
Clin Endocrinol (Oxf) 66:21-6. 2007..We have identified a pair of siblings with RMS attributable to compound heterozygosity for two insulin receptor mutations, one previously unreported, and have characterized the novel receptor mutation functionally...
Founder effect in the Horn of Africa for an insulin receptor mutation that may impair receptor recyclingE Raffan
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital B289, Cambridge, CB2 0QR, UK
Diabetologia 54:1057-65. 2011..We aimed to investigate a possible genetic founder effect, and to study the mechanism of loss of function of the mutant receptor...- Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosisRobert K Semple
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
J Clin Invest 119:315-22. 2009.... - From bending DNA to diabetes: the curious case of HMGA1Robert K Semple
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Cambridge CB2 0QR, UK
J Biol 8:64. 2009..A study in BMC Biology now suggests that changes in circulating retinol binding protein partly account for this paradox... 
The recent genetics of hypogonadotrophic hypogonadism - novel insights and new questionsRobert K Semple
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
Clin Endocrinol (Oxf) 72:427-35. 2010..This review summarises current understanding of the genetic architecture of HH, as well as its diagnostic and mechanistic implications...- Paradoxical elevation of high-molecular weight adiponectin in acquired extreme insulin resistance due to insulin receptor antibodiesRobert K Semple
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
Diabetes 56:1712-7. 2007.... - Elevated plasma adiponectin in humans with genetically defective insulin receptorsR K Semple
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Cambridge CB2 2QR, United Kingdom
J Clin Endocrinol Metab 91:3219-23. 2006..Adiponectin has been suggested to play a role in the etiopathogenesis of at least some forms of insulin resistance, in part based on a strong correlation between plasma levels of adiponectin and measures of insulin sensitivity... - Neurokinin B and its receptor in hypogonadotropic hypogonadismRobert K Semple
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, UK
Front Horm Res 39:133-41. 2010..We review the human genetics of NKB and its receptor, and discuss the future work required to elucidate their precise role in the regulation of human GnRH secretion... - A dominant negative human peroxisome proliferator-activated receptor (PPAR){alpha} is a constitutive transcriptional corepressor and inhibits signaling through all PPAR isoformsR K Semple
Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge CB2 2QR, United Kingdom
Endocrinology 146:1871-82. 2005..These findings may have implications for the pathogenesis of human syndromes resulting from mutations in this family of transcription factors... - Two novel missense mutations in g protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadismR K Semple
Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge CB2 2QR, United Kingdom
J Clin Endocrinol Metab 90:1849-55. 2005..These novel mutations provide further evidence that human HH may be caused by loss-of-function mutations in GPR54... - Genetic syndromes of severe insulin resistanceRobert K Semple
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
Endocr Rev 32:498-514. 2011..We now review recent developments in understanding of genetic forms of severe insulin resistance and/or lipodystrophy and suggest a revised classification based on growing knowledge of the underlying pathophysiology... - Plasma adiponectin as a marker of insulin receptor dysfunction: clinical utility in severe insulin resistanceRobert K Semple
Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
Diabetes Care 31:977-9. 2008..Our previous observation of paradoxical hyperadiponectinemia in insulin receptoropathy provides a possible basis for a simpler and cheaper screening test... - Treatment with recombinant human insulin-like growth factor (rhIGF)-I/rhIGF binding protein-3 complex improves metabolic control in subjects with severe insulin resistanceFiona M Regan
University of Cambridge, Department of Pediatrics, Cambridge, United Kingdom
J Clin Endocrinol Metab 95:2113-22. 2010..We report clinical and physiological outcomes after adjunctive therapy with rhIGF-I/rhIGFBP-3 in five subjects with SIR... - Metabolic insights from extreme human insulin resistance phenotypesAnna Stears
Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, University of Cambridge, UK
Best Pract Res Clin Endocrinol Metab 26:145-57. 2012.... - Mitochondrial dysfunction in patients with primary congenital insulin resistanceAlison Sleigh
Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom
J Clin Invest 121:2457-61. 2011.... - What is the best management strategy for patients with severe insulin resistance?Robert K Semple
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Cambridge CB2 0QQ, UK
Clin Endocrinol (Oxf) 73:286-90. 2010..Thus, management of these patients remains largely empirical, and there is a pressing need to collate data centrally to optimize treatment algorithms... 
Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathwaysLigang Zhou
Department of Clinical Biochemistry, Addenbrooke s Hospital, University of Cambridge, Cambridge CB2 2QQ, UK
Cell Metab 6:398-405. 2007....- Complement abnormalities in acquired lipodystrophy revisitedDavid B Savage
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom
J Clin Endocrinol Metab 94:10-6. 2009.... - The human lipodystrophy gene BSCL2/seipin may be essential for normal adipocyte differentiationVictoria A Payne
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, UK
Diabetes 57:2055-60. 2008..Therefore, we examined whether BSCL2 is involved in the regulation of adipocyte differentiation and the mechanism whereby pathogenic mutations in BSCL2 cause lipodystrophy... - Next generation sequencing--implications for clinical practiceEleanor Raffan
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Box 289, Addenbrooke s Hospital, Cambridge CB2 0QQ, UK
Br Med Bull 99:53-71. 2011..Consequently, many patients with genetic syndromes remain without a specific diagnosis... - Recent insights into fatty liver, metabolic dyslipidaemia and their links to insulin resistanceDavid B Savage
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
Curr Opin Lipidol 21:329-36. 2010..To summarize recent research into the mechanisms linking insulin resistance, nonalcoholic fatty liver disease and metabolic dyslipidaemia... - A truncation mutation in TBC1D4 in a family with acanthosis nigricans and postprandial hyperinsulinemiaSatya Dash
Departments of Medicine and Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
Proc Natl Acad Sci U S A 106:9350-5. 2009..This family provides unique genetic evidence of TBC1D4 involvement in human insulin action... - A clinical approach to severe insulin resistanceDavid B Savage
Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK
Endocr Dev 11:122-32. 2007..In the absence of a specific diagnosis and therapy, metformin is a useful insulin sensitizer and should be used in conjunction with aggressive diet and exercise interventions... - Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profileTuomas O Kilpeläinen
Medical Research Council MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK
Nat Genet 43:753-60. 2011..Our findings provide new insights into adiposity and insulin resistance... - Hypoadiponectinemia--cause or consequence of human "insulin resistance"?Joshua R Cook
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Treatment Centre, Addenbrooke s Hospital, Hills Road, Cambridge CB2 OQQ, United Kingdom
J Clin Endocrinol Metab 95:1544-54. 2010..It has been suggested that pharmacological strategies aimed at augmenting adiponectin levels or action may generate novel insulin-sensitizing drugs... - IGF-I treatment of insulin resistanceAnna McDonald
University of Cambridge, Department of Paediatrics, Box 116, Addenbrookes Hospital, Hills Road, Cambridge, CB2 2QQ, UK
Eur J Endocrinol 157:S51-6. 2007.... - Genetic defects in human pericentrin are associated with severe insulin resistance and diabetesIsabel Huang-Doran
Institute of Metabolic Science, Addenbrooke s Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, UK
Diabetes 60:925-35. 2011..We thus set out to determine the prevalence of diabetes and insulin resistance among patients with PCNT defects and examined the effects of pericentrin depletion on insulin action using 3T3-L1 adipocytes as a model system... - Perilipin deficiency and autosomal dominant partial lipodystrophySheetal Gandotra
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, United Kingdom
N Engl J Med 364:740-8. 2011..These findings define a novel dominant form of inherited lipodystrophy and highlight the serious metabolic consequences of a primary defect in the formation of lipid droplets in adipose tissue... - PPAR gamma and human metabolic diseaseRobert K Semple
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom
J Clin Invest 116:581-9. 2006.... - ETO/MTG8 is an inhibitor of C/EBPbeta activity and a regulator of early adipogenesisJustin J Rochford
Department of Clinical Biochemistry, University of Cambridge, Box 232, Level 4, Addenbrooke s Hospital, Hills Rd, Cambridge CB2 2QR, United Kingdom
Mol Cell Biol 24:9863-72. 2004..These findings define, for the first time, a molecular role for ETO in normal physiology as an inhibitor of C/EBPbeta and a novel regulator of early adipogenesis... - Severe hypo-alpha-lipoproteinemia during treatment with rosiglitazoneAnita Sarker
Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge, UK
Diabetes Care 27:2577-80. 2004..Until the frequency of this adverse reaction is clearer, it would seem advisable to ensure that plasma HDL cholesterol is documented before and rechecked after commencement of thiazolidinedione therapy... - Severe insulin resistance due to anti-insulin antibodies: response to plasma exchange and immunosuppressive therapyJ R Greenfield
Institute of Metabolic Science and Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge, UK
Diabet Med 26:79-82. 2009..This case suggests that clinicians should be alert to the possibility of insulin resistance due to anti-insulin antibodies and that immunosuppression in this situation may be a valuable therapeutic option... - Expression of the thermogenic nuclear hormone receptor coactivator PGC-1alpha is reduced in the adipose tissue of morbidly obese subjectsR K Semple
Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
Int J Obes Relat Metab Disord 28:176-9. 2004.... - The effects of neurokinin B upon gonadotrophin release in male rodentsM P Corander
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Treatment Centre, Addenbrooke s Hospital, Cambridge, UK
J Neuroendocrinol 22:181-7. 2010..In male rodent models, NKB and kisspeptin have different effects upon gonadotrophin release and appear to interact in a complex manner... - Analysis of genetic variation in Akt2/PKB-beta in severe insulin resistance, lipodystrophy, type 2 diabetes, and related metabolic phenotypesKaren Tan
Metabolic Disease Group, Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, U K
Diabetes 56:714-9. 2007..Furthermore, genetic variation in and around the AKT2 locus is unlikely to contribute significantly to the risk of type 2 diabetes or related intermediate metabolic traits in U.K. populations... - Mutations in the pericentrin (PCNT) gene cause primordial dwarfismAnita Rauch
Institute of Human Genetics, University Hospital Erlangen, Friedrich Alexander University Erlangen Nuremberg, Erlangen, Germany
Science 319:816-9. 2008..Absence of PCNT results in disorganized mitotic spindles and missegregation of chromosomes. Mutations in related genes are known to cause primary microcephaly (MCPH1, CDK5RAP2, ASPM, and CENPJ)...