Search Results - (Author, Cooperation:L. C. Groop)

Showing 1 - 16 results of 16, query time: 0.41s Refine Results
  1. 1
    A. E. Locke ; B. Kahali ; S. I. Berndt ; A. E. Justice ; T. H. Pers ; F. R. Day ; C. Powell ; S. Vedantam ; M. L. Buchkovich ; J. Yang ; D. C. Croteau-Chonka ; T. Esko ; T. Fall ; T. Ferreira ; S. Gustafsson ; Z. Kutalik ; J. Luan ; R. Magi ; J. C. Randall ; T. W. Winkler ; A. R. Wood ; T. Workalemahu ; J. D. Faul ; J. A. Smith ; J. Hua Zhao ; W. Zhao ; J. Chen ; R. Fehrmann ; A. K. Hedman ; J. Karjalainen ; E. M. Schmidt ; D. Absher ; N. Amin ; D. Anderson ; M. Beekman ; J. L. Bolton ; J. L. Bragg-Gresham ; S. Buyske ; A. Demirkan ; G. Deng ; G. B. Ehret ; B. Feenstra ; M. F. Feitosa ; K. Fischer ; A. Goel ; J. Gong ; A. U. Jackson ; S. Kanoni ; M. E. Kleber ; K. Kristiansson ; U. Lim ; V. Lotay ; M. Mangino ; I. Mateo Leach ; C. Medina-Gomez ; S. E. Medland ; M. A. Nalls ; C. D. Palmer ; D. Pasko ; S. Pechlivanis ; M. J. Peters ; I. Prokopenko ; D. Shungin ; A. Stancakova ; R. J. Strawbridge ; Y. Ju Sung ; T. Tanaka ; A. Teumer ; S. Trompet ; S. W. van der Laan ; J. van Setten ; J. V. Van Vliet-Ostaptchouk ; Z. Wang ; L. Yengo ; W. Zhang ; A. Isaacs ; E. Albrecht ; J. Arnlov ; G. M. Arscott ; A. P. Attwood ; S. Bandinelli ; A. Barrett ; I. N. Bas ; C. Bellis ; A. J. Bennett ; C. Berne ; R. Blagieva ; M. Bluher ; S. Bohringer ; L. L. Bonnycastle ; Y. Bottcher ; H. A. Boyd ; M. Bruinenberg ; I. H. Caspersen ; Y. D. Ida Chen ; R. Clarke ; E. W. Daw ; A. J. de Craen ; G. Delgado ; M. Dimitriou ; A. S. Doney ; N. Eklund ; K. Estrada ; E. Eury ; L. Folkersen ; R. M. Fraser ; M. E. Garcia ; F. Geller ; V. Giedraitis ; B. Gigante ; A. S. Go ; A. Golay ; A. H. Goodall ; S. D. Gordon ; M. Gorski ; H. J. Grabe ; H. Grallert ; T. B. Grammer ; J. Grassler ; H. Gronberg ; C. J. Groves ; G. Gusto ; J. Haessler ; P. Hall ; T. Haller ; G. Hallmans ; C. A. Hartman ; M. Hassinen ; C. Hayward ; N. L. Heard-Costa ; Q. Helmer ; C. Hengstenberg ; O. Holmen ; J. J. Hottenga ; A. L. James ; J. M. Jeff ; A. Johansson ; J. Jolley ; T. Juliusdottir ; L. Kinnunen ; W. Koenig ; M. Koskenvuo ; W. Kratzer ; J. Laitinen ; C. Lamina ; K. Leander ; N. R. Lee ; P. Lichtner ; L. Lind ; J. Lindstrom ; K. Sin Lo ; S. Lobbens ; R. Lorbeer ; Y. Lu ; F. Mach ; P. K. Magnusson ; A. Mahajan ; W. L. McArdle ; S. McLachlan ; C. Menni ; S. Merger ; E. Mihailov ; L. Milani ; A. Moayyeri ; K. L. Monda ; M. A. Morken ; A. Mulas ; G. Muller ; M. Muller-Nurasyid ; A. W. Musk ; R. Nagaraja ; M. M. Nothen ; I. M. Nolte ; S. Pilz ; N. W. Rayner ; F. Renstrom ; R. Rettig ; J. S. Ried ; S. Ripke ; N. R. Robertson ; L. M. Rose ; S. Sanna ; H. Scharnagl ; S. Scholtens ; F. R. Schumacher ; W. R. Scott ; T. Seufferlein ; J. Shi ; A. Vernon Smith ; J. Smolonska ; A. V. Stanton ; V. Steinthorsdottir ; K. Stirrups ; H. M. Stringham ; J. Sundstrom ; M. A. Swertz ; A. J. Swift ; A. C. Syvanen ; S. T. Tan ; B. O. Tayo ; B. Thorand ; G. Thorleifsson ; J. P. Tyrer ; H. W. Uh ; L. Vandenput ; F. C. Verhulst ; S. H. Vermeulen ; N. Verweij ; J. M. Vonk ; L. L. Waite ; H. R. Warren ; D. Waterworth ; M. N. Weedon ; L. R. Wilkens ; C. Willenborg ; T. Wilsgaard ; M. K. Wojczynski ; A. Wong ; A. F. Wright ; Q. Zhang ; E. P. Brennan ; M. Choi ; Z. Dastani ; A. W. Drong ; P. Eriksson ; A. Franco-Cereceda ; J. R. Gadin ; A. G. Gharavi ; M. E. Goddard ; R. E. Handsaker ; J. Huang ; F. Karpe ; S. Kathiresan ; S. Keildson ; K. Kiryluk ; M. Kubo ; J. Y. Lee ; L. Liang ; R. P. Lifton ; B. Ma ; S. A. McCarroll ; A. J. McKnight ; J. L. Min ; M. F. Moffatt ; G. W. Montgomery ; J. M. Murabito ; G. Nicholson ; D. R. Nyholt ; Y. Okada ; J. R. Perry ; R. Dorajoo ; E. Reinmaa ; R. M. Salem ; N. Sandholm ; R. A. Scott ; L. Stolk ; A. Takahashi ; F. M. Van't Hooft ; A. A. Vinkhuyzen ; H. J. Westra ; W. Zheng ; K. T. Zondervan ; A. C. Heath ; D. Arveiler ; S. J. Bakker ; J. Beilby ; R. N. Bergman ; J. Blangero ; P. Bovet ; H. Campbell ; M. J. Caulfield ; G. Cesana ; A. Chakravarti ; D. I. Chasman ; P. S. Chines ; F. S. Collins ; D. C. Crawford ; L. A. Cupples ; D. Cusi ; J. Danesh ; U. de Faire ; H. M. den Ruijter ; A. F. Dominiczak ; R. Erbel ; J. Erdmann ; J. G. Eriksson ; M. Farrall ; S. B. Felix ; E. Ferrannini ; J. Ferrieres ; I. Ford ; N. G. Forouhi ; T. Forrester ; O. H. Franco ; R. T. Gansevoort ; P. V. Gejman ; C. Gieger ; O. Gottesman ; V. Gudnason ; U. Gyllensten ; A. S. Hall ; T. B. Harris ; A. T. Hattersley ; A. A. Hicks ; L. A. Hindorff ; A. D. Hingorani ; A. Hofman ; G. Homuth ; G. K. Hovingh ; S. E. Humphries ; S. C. Hunt ; E. Hypponen ; T. Illig ; K. B. Jacobs ; M. R. Jarvelin ; K. H. Jockel ; B. Johansen ; P. Jousilahti ; J. W. Jukema ; A. M. Jula ; J. Kaprio ; J. J. Kastelein ; S. M. Keinanen-Kiukaanniemi ; L. A. Kiemeney ; P. Knekt ; J. S. Kooner ; C. Kooperberg ; P. Kovacs ; A. T. Kraja ; M. Kumari ; J. Kuusisto ; T. A. Lakka ; C. Langenberg ; L. Le Marchand ; T. Lehtimaki ; V. Lyssenko ; S. Mannisto ; A. Marette ; T. C. Matise ; C. A. McKenzie ; B. McKnight ; F. L. Moll ; A. D. Morris ; A. P. Morris ; J. C. Murray ; M. Nelis ; C. Ohlsson ; A. J. Oldehinkel ; K. K. Ong ; P. A. Madden ; G. Pasterkamp ; J. F. Peden ; A. Peters ; D. S. Postma ; P. P. Pramstaller ; J. F. Price ; L. Qi ; O. T. Raitakari ; T. Rankinen ; D. C. Rao ; T. K. Rice ; P. M. Ridker ; J. D. Rioux ; M. D. Ritchie ; I. Rudan ; V. Salomaa ; N. J. Samani ; J. Saramies ; M. A. Sarzynski ; H. Schunkert ; P. E. Schwarz ; P. Sever ; A. R. Shuldiner ; J. Sinisalo ; R. P. Stolk ; K. Strauch ; A. Tonjes ; D. A. Tregouet ; A. Tremblay ; E. Tremoli ; J. Virtamo ; M. C. Vohl ; U. Volker ; G. Waeber ; G. Willemsen ; J. C. Witteman ; M. C. Zillikens ; L. S. Adair ; P. Amouyel ; F. W. Asselbergs ; T. L. Assimes ; M. Bochud ; B. O. Boehm ; E. Boerwinkle ; S. R. Bornstein ; E. P. Bottinger ; C. Bouchard ; S. Cauchi ; J. C. Chambers ; S. J. Chanock ; R. S. Cooper ; P. I. de Bakker ; G. Dedoussis ; L. Ferrucci ; P. W. Franks ; P. Froguel ; L. C. Groop ; C. A. Haiman ; A. Hamsten ; J. Hui ; D. J. Hunter ; K. Hveem ; R. C. Kaplan ; M. Kivimaki ; D. Kuh ; M. Laakso ; Y. Liu ; N. G. Martin ; W. Marz ; M. Melbye ; A. Metspalu ; S. Moebus ; P. B. Munroe ; I. Njolstad ; B. A. Oostra ; C. N. Palmer ; N. L. Pedersen ; M. Perola ; L. Perusse ; U. Peters ; C. Power ; T. Quertermous ; R. Rauramaa ; F. Rivadeneira ; T. E. Saaristo ; D. Saleheen ; N. Sattar ; E. E. Schadt ; D. Schlessinger ; P. E. Slagboom ; H. Snieder ; T. D. Spector ; U. Thorsteinsdottir ; M. Stumvoll ; J. Tuomilehto ; A. G. Uitterlinden ; M. Uusitupa ; P. van der Harst ; M. Walker ; H. Wallaschofski ; N. J. Wareham ; H. Watkins ; D. R. Weir ; H. E. Wichmann ; J. F. Wilson ; P. Zanen ; I. B. Borecki ; P. Deloukas ; C. S. Fox ; I. M. Heid ; J. R. O'Connell ; D. P. Strachan ; K. Stefansson ; C. M. van Duijn ; G. R. Abecasis ; L. Franke ; T. M. Frayling ; M. I. McCarthy ; P. M. Visscher ; A. Scherag ; C. J. Willer ; M. Boehnke ; K. L. Mohlke ; C. M. Lindgren ; J. S. Beckmann ; I. Barroso ; K. E. North ; E. Ingelsson ; J. N. Hirschhorn ; R. J. Loos ; E. K. Speliotes
    Nature Publishing Group (NPG)
    Published 2015
    Staff View
    Publication Date:
    2015-02-13
    Publisher:
    Nature Publishing Group (NPG)
    Print ISSN:
    0028-0836
    Electronic ISSN:
    1476-4687
    Topics:
    Biology
    Chemistry and Pharmacology
    Medicine
    Natural Sciences in General
    Physics
    Keywords:
    Adipogenesis/genetics ; Adiposity/genetics ; Age Factors ; *Body Mass Index ; Continental Population Groups/genetics ; Energy Metabolism/genetics ; Europe/ethnology ; Female ; Genetic Predisposition to Disease/genetics ; *Genome-Wide Association Study ; Glutamic Acid/metabolism ; Humans ; Insulin/metabolism/secretion ; Male ; Obesity/*genetics/*metabolism ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; Synapses/metabolism
    Published by:
    http://www.nature.com/

    Latest Papers from Table of Contents or Articles in Press
  2. 2
    D. Shungin ; T. W. Winkler ; D. C. Croteau-Chonka ; T. Ferreira ; A. E. Locke ; R. Magi ; R. J. Strawbridge ; T. H. Pers ; K. Fischer ; A. E. Justice ; T. Workalemahu ; J. M. Wu ; M. L. Buchkovich ; N. L. Heard-Costa ; T. S. Roman ; A. W. Drong ; C. Song ; S. Gustafsson ; F. R. Day ; T. Esko ; T. Fall ; Z. Kutalik ; J. Luan ; J. C. Randall ; A. Scherag ; S. Vedantam ; A. R. Wood ; J. Chen ; R. Fehrmann ; J. Karjalainen ; B. Kahali ; C. T. Liu ; E. M. Schmidt ; D. Absher ; N. Amin ; D. Anderson ; M. Beekman ; J. L. Bragg-Gresham ; S. Buyske ; A. Demirkan ; G. B. Ehret ; M. F. Feitosa ; A. Goel ; A. U. Jackson ; T. Johnson ; M. E. Kleber ; K. Kristiansson ; M. Mangino ; I. Mateo Leach ; C. Medina-Gomez ; C. D. Palmer ; D. Pasko ; S. Pechlivanis ; M. J. Peters ; I. Prokopenko ; A. Stancakova ; Y. Ju Sung ; T. Tanaka ; A. Teumer ; J. V. Van Vliet-Ostaptchouk ; L. Yengo ; W. Zhang ; E. Albrecht ; J. Arnlov ; G. M. Arscott ; S. Bandinelli ; A. Barrett ; C. Bellis ; A. J. Bennett ; C. Berne ; M. Bluher ; S. Bohringer ; F. Bonnet ; Y. Bottcher ; M. Bruinenberg ; D. B. Carba ; I. H. Caspersen ; R. Clarke ; E. W. Daw ; J. Deelen ; E. Deelman ; G. Delgado ; A. S. Doney ; N. Eklund ; M. R. Erdos ; K. Estrada ; E. Eury ; N. Friedrich ; M. E. Garcia ; V. Giedraitis ; B. Gigante ; A. S. Go ; A. Golay ; H. Grallert ; T. B. Grammer ; J. Grassler ; J. Grewal ; C. J. Groves ; T. Haller ; G. Hallmans ; C. A. Hartman ; M. Hassinen ; C. Hayward ; K. Heikkila ; K. H. Herzig ; Q. Helmer ; H. L. Hillege ; O. Holmen ; S. C. Hunt ; A. Isaacs ; T. Ittermann ; A. L. James ; I. Johansson ; T. Juliusdottir ; I. P. Kalafati ; L. Kinnunen ; W. Koenig ; I. K. Kooner ; W. Kratzer ; C. Lamina ; K. Leander ; N. R. Lee ; P. Lichtner ; L. Lind ; J. Lindstrom ; S. Lobbens ; M. Lorentzon ; F. Mach ; P. K. Magnusson ; A. Mahajan ; W. L. McArdle ; C. Menni ; S. Merger ; E. Mihailov ; L. Milani ; R. Mills ; A. Moayyeri ; K. L. Monda ; S. P. Mooijaart ; T. W. Muhleisen ; A. Mulas ; G. Muller ; M. Muller-Nurasyid ; R. Nagaraja ; M. A. Nalls ; N. Narisu ; N. Glorioso ; I. M. Nolte ; M. Olden ; N. W. Rayner ; F. Renstrom ; J. S. Ried ; N. R. Robertson ; L. M. Rose ; S. Sanna ; H. Scharnagl ; S. Scholtens ; B. Sennblad ; T. Seufferlein ; C. M. Sitlani ; A. Vernon Smith ; K. Stirrups ; H. M. Stringham ; J. Sundstrom ; M. A. Swertz ; A. J. Swift ; A. C. Syvanen ; B. O. Tayo ; B. Thorand ; G. Thorleifsson ; A. Tomaschitz ; C. Troffa ; F. V. van Oort ; N. Verweij ; J. M. Vonk ; L. L. Waite ; R. Wennauer ; T. Wilsgaard ; M. K. Wojczynski ; A. Wong ; Q. Zhang ; J. Hua Zhao ; E. P. Brennan ; M. Choi ; P. Eriksson ; L. Folkersen ; A. Franco-Cereceda ; A. G. Gharavi ; A. K. Hedman ; M. F. Hivert ; J. Huang ; S. Kanoni ; F. Karpe ; S. Keildson ; K. Kiryluk ; L. Liang ; R. P. Lifton ; B. Ma ; A. J. McKnight ; R. McPherson ; A. Metspalu ; J. L. Min ; M. F. Moffatt ; G. W. Montgomery ; J. M. Murabito ; G. Nicholson ; D. R. Nyholt ; C. Olsson ; J. R. Perry ; E. Reinmaa ; R. M. Salem ; N. Sandholm ; E. E. Schadt ; R. A. Scott ; L. Stolk ; E. E. Vallejo ; H. J. Westra ; K. T. Zondervan ; P. Amouyel ; D. Arveiler ; S. J. Bakker ; J. Beilby ; R. N. Bergman ; J. Blangero ; M. J. Brown ; M. Burnier ; H. Campbell ; A. Chakravarti ; P. S. Chines ; S. Claudi-Boehm ; F. S. Collins ; D. C. Crawford ; J. Danesh ; U. de Faire ; E. J. de Geus ; M. Dorr ; R. Erbel ; J. G. Eriksson ; M. Farrall ; E. Ferrannini ; J. Ferrieres ; N. G. Forouhi ; T. Forrester ; O. H. Franco ; R. T. Gansevoort ; C. Gieger ; V. Gudnason ; C. A. Haiman ; T. B. Harris ; A. T. Hattersley ; M. Heliovaara ; A. A. Hicks ; A. D. Hingorani ; W. Hoffmann ; A. Hofman ; G. Homuth ; S. E. Humphries ; E. Hypponen ; T. Illig ; M. R. Jarvelin ; B. Johansen ; P. Jousilahti ; A. M. Jula ; J. Kaprio ; F. Kee ; S. M. Keinanen-Kiukaanniemi ; J. S. Kooner ; C. Kooperberg ; P. Kovacs ; A. T. Kraja ; M. Kumari ; K. Kuulasmaa ; J. Kuusisto ; T. A. Lakka ; C. Langenberg ; L. Le Marchand ; T. Lehtimaki ; V. Lyssenko ; S. Mannisto ; A. Marette ; T. C. Matise ; C. A. McKenzie ; B. McKnight ; A. W. Musk ; S. Mohlenkamp ; A. D. Morris ; M. Nelis ; C. Ohlsson ; A. J. Oldehinkel ; K. K. Ong ; L. J. Palmer ; B. W. Penninx ; A. Peters ; P. P. Pramstaller ; O. T. Raitakari ; T. Rankinen ; D. C. Rao ; T. K. Rice ; P. M. Ridker ; M. D. Ritchie ; I. Rudan ; V. Salomaa ; N. J. Samani ; J. Saramies ; M. A. Sarzynski ; P. E. Schwarz ; A. R. Shuldiner ; J. A. Staessen ; V. Steinthorsdottir ; R. P. Stolk ; K. Strauch ; A. Tonjes ; A. Tremblay ; E. Tremoli ; M. C. Vohl ; U. Volker ; P. Vollenweider ; J. F. Wilson ; J. C. Witteman ; L. S. Adair ; M. Bochud ; B. O. Boehm ; S. R. Bornstein ; C. Bouchard ; S. Cauchi ; M. J. Caulfield ; J. C. Chambers ; D. I. Chasman ; R. S. Cooper ; G. Dedoussis ; L. Ferrucci ; P. Froguel ; H. J. Grabe ; A. Hamsten ; J. Hui ; K. Hveem ; K. H. Jockel ; M. Kivimaki ; D. Kuh ; M. Laakso ; Y. Liu ; W. Marz ; P. B. Munroe ; I. Njolstad ; B. A. Oostra ; C. N. Palmer ; N. L. Pedersen ; M. Perola ; L. Perusse ; U. Peters ; C. Power ; T. Quertermous ; R. Rauramaa ; F. Rivadeneira ; T. E. Saaristo ; D. Saleheen ; J. Sinisalo ; P. E. Slagboom ; H. Snieder ; T. D. Spector ; U. Thorsteinsdottir ; M. Stumvoll ; J. Tuomilehto ; A. G. Uitterlinden ; M. Uusitupa ; P. van der Harst ; G. Veronesi ; M. Walker ; N. J. Wareham ; H. Watkins ; H. E. Wichmann ; G. R. Abecasis ; T. L. Assimes ; S. I. Berndt ; M. Boehnke ; I. B. Borecki ; P. Deloukas ; L. Franke ; T. M. Frayling ; L. C. Groop ; D. J. Hunter ; R. C. Kaplan ; J. R. O'Connell ; L. Qi ; D. Schlessinger ; D. P. Strachan ; K. Stefansson ; C. M. van Duijn ; C. J. Willer ; P. M. Visscher ; J. Yang ; J. N. Hirschhorn ; M. C. Zillikens ; M. I. McCarthy ; E. K. Speliotes ; K. E. North ; C. S. Fox ; I. Barroso ; P. W. Franks ; E. Ingelsson ; I. M. Heid ; R. J. Loos ; L. A. Cupples ; A. P. Morris ; C. M. Lindgren ; K. L. Mohlke
    Nature Publishing Group (NPG)
    Published 2015
    Staff View
    Publication Date:
    2015-02-13
    Publisher:
    Nature Publishing Group (NPG)
    Print ISSN:
    0028-0836
    Electronic ISSN:
    1476-4687
    Topics:
    Biology
    Chemistry and Pharmacology
    Medicine
    Natural Sciences in General
    Physics
    Keywords:
    Adipocytes/metabolism ; Adipogenesis/genetics ; Adipose Tissue/*metabolism ; Age Factors ; *Body Fat Distribution ; Body Mass Index ; Continental Population Groups/genetics ; Epigenesis, Genetic ; Europe/ethnology ; Female ; Genome, Human/genetics ; *Genome-Wide Association Study ; Humans ; Insulin/*metabolism ; Insulin Resistance/genetics ; Male ; Models, Biological ; Neovascularization, Physiologic/genetics ; Obesity/genetics ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/*genetics ; Sex Characteristics ; Transcription, Genetic/genetics ; Waist-Hip Ratio
    Published by:
    http://www.nature.com/

    Latest Papers from Table of Contents or Articles in Press
  3. 3
    J. Yang ; R. J. Loos ; J. E. Powell ; S. E. Medland ; E. K. Speliotes ; D. I. Chasman ; L. M. Rose ; G. Thorleifsson ; V. Steinthorsdottir ; R. Magi ; L. Waite ; A. V. Smith ; L. M. Yerges-Armstrong ; K. L. Monda ; D. Hadley ; A. Mahajan ; G. Li ; K. Kapur ; V. Vitart ; J. E. Huffman ; S. R. Wang ; C. Palmer ; T. Esko ; K. Fischer ; J. H. Zhao ; A. Demirkan ; A. Isaacs ; M. F. Feitosa ; J. Luan ; N. L. Heard-Costa ; C. White ; A. U. Jackson ; M. Preuss ; A. Ziegler ; J. Eriksson ; Z. Kutalik ; F. Frau ; I. M. Nolte ; J. V. Van Vliet-Ostaptchouk ; J. J. Hottenga ; K. B. Jacobs ; N. Verweij ; A. Goel ; C. Medina-Gomez ; K. Estrada ; J. L. Bragg-Gresham ; S. Sanna ; C. Sidore ; J. Tyrer ; A. Teumer ; I. Prokopenko ; M. Mangino ; C. M. Lindgren ; T. L. Assimes ; A. R. Shuldiner ; J. Hui ; J. P. Beilby ; W. L. McArdle ; P. Hall ; T. Haritunians ; L. Zgaga ; I. Kolcic ; O. Polasek ; T. Zemunik ; B. A. Oostra ; M. J. Junttila ; H. Gronberg ; S. Schreiber ; A. Peters ; A. A. Hicks ; J. Stephens ; N. S. Foad ; J. Laitinen ; A. Pouta ; M. Kaakinen ; G. Willemsen ; J. M. Vink ; S. H. Wild ; G. Navis ; F. W. Asselbergs ; G. Homuth ; U. John ; C. Iribarren ; T. Harris ; L. Launer ; V. Gudnason ; J. R. O'Connell ; E. Boerwinkle ; G. Cadby ; L. J. Palmer ; A. L. James ; A. W. Musk ; E. Ingelsson ; B. M. Psaty ; J. S. Beckmann ; G. Waeber ; P. Vollenweider ; C. Hayward ; A. F. Wright ; I. Rudan ; L. C. Groop ; A. Metspalu ; K. T. Khaw ; C. M. van Duijn ; I. B. Borecki ; M. A. Province ; N. J. Wareham ; J. C. Tardif ; H. V. Huikuri ; L. A. Cupples ; L. D. Atwood ; C. S. Fox ; M. Boehnke ; F. S. Collins ; K. L. Mohlke ; J. Erdmann ; H. Schunkert ; C. Hengstenberg ; K. Stark ; M. Lorentzon ; C. Ohlsson ; D. Cusi ; J. A. Staessen ; M. M. Van der Klauw ; P. P. Pramstaller ; S. Kathiresan ; J. D. Jolley ; S. Ripatti ; M. R. Jarvelin ; E. J. de Geus ; D. I. Boomsma ; B. Penninx ; J. F. Wilson ; H. Campbell ; S. J. Chanock ; P. van der Harst ; A. Hamsten ; H. Watkins ; A. Hofman ; J. C. Witteman ; M. C. Zillikens ; A. G. Uitterlinden ; F. Rivadeneira ; L. A. Kiemeney ; S. H. Vermeulen ; G. R. Abecasis ; D. Schlessinger ; S. Schipf ; M. Stumvoll ; A. Tonjes ; T. D. Spector ; K. E. North ; G. Lettre ; M. I. McCarthy ; S. I. Berndt ; A. C. Heath ; P. A. Madden ; D. R. Nyholt ; G. W. Montgomery ; N. G. Martin ; B. McKnight ; D. P. Strachan ; W. G. Hill ; H. Snieder ; P. M. Ridker ; U. Thorsteinsdottir ; K. Stefansson ; T. M. Frayling ; J. N. Hirschhorn ; M. E. Goddard ; P. M. Visscher
    Nature Publishing Group (NPG)
    Published 2012
    Staff View
    Publication Date:
    2012-09-18
    Publisher:
    Nature Publishing Group (NPG)
    Print ISSN:
    0028-0836
    Electronic ISSN:
    1476-4687
    Topics:
    Biology
    Chemistry and Pharmacology
    Medicine
    Natural Sciences in General
    Physics
    Keywords:
    Body Height/genetics ; *Body Mass Index ; Co-Repressor Proteins ; Female ; *Genetic Variation ; Genome-Wide Association Study ; Humans ; Male ; Nerve Tissue Proteins/genetics ; *Phenotype ; Polymorphism, Single Nucleotide ; Proteins/*genetics ; Repressor Proteins/genetics
    Published by:
    http://www.nature.com/

    Latest Papers from Table of Contents or Articles in Press
  4. 4
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Genetics ; DNA polymorphism ; glucose ; phosphorylation ; glycolysis ; chromosome 2 ; insulin resistance
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Type 2 (non-insulin-dependent) diabetes mellitus is characterized by decreased levels of glucose 6-phosphate in skeletal muscle. It has been suggested that the lower concentrations of glucose 6-phosphate contribute to the defect in glucose metabolism noted in muscle tissue of subjects with Type 2 diabetes or subjects at increased risk of developing Type 2 diabetes. Lower levels of glucose 6-phosphate could be due to a defect in glucose uptake, or phosphorylation, or both. Hexokinase II is the isozyme of hexokinase that is expressed in skeletal muscle and is responsible for catalysing the phosphorylation of glucose in this tissue. The recent demonstration that mutations in another member of this family of glucose phosphorylating enzymes, glucokinase, can lead to the development of Type 2 diabetes prompted us to begin to examine the possible role of hexokinase II in the development of this genetically heterogeneous disorder. As a first step, we have cloned the human hexokinase II gene (HK2) and mapped it to human chromosome 2, band p13.1, by fluorescence in situ hybridization to metaphase chromosomes. In addition, we have identified and characterized a simple tandem repeat DNA polymorphism in HK2 and used this DNA polymorphism to localize this gene within the genetic linkage map of chromosome 2.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00400809

    Articles: DFG German National Licenses
  5. 5
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Microalbuminuria ; insulin resistance syndrome ; insulin sensitivity ; euglycaemic hyperinsulinaemic clamp
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Microalbuminuria has recently been associated with insulin resistance in both insulin-dependent and non-insulin-dependent (NIDDM) diabetes mellitus. To establish whether microalbuminuria in non-diabetic subjects as well is associated with insulin resistance and associated abnormalities in glucose and lipid metabolism, oral glucose tolerance tests were performed with measurement of urinary albumin excretion rate, lipids and lipoproteins in 582 male non-diabetic first-degree relatives of patients with NIDDM. In addition, insulin sensitivity was assessed in 20 of these subjects with the euglycaemic hyperinsulinaemic clamp technique. Abnormal albumin excretion rate (AER), defined as AER 15–200 Μg/min, was associated with higher systolic blood pressure (p〈0.05), higher fasting glucose values (p〈0.05), lower HDL-cholesterol (p〈0.05) and lower apolipoprotein A-I (p〈0.05) concentrations than observed in subjects with normal AER. The rate of glucose metabolism was lower in subjects with abnormal compared to subjects with normal albumin excretion rate (38.0±2.8 vs 47.3±2.4 Μmol·kg lean body mass−1. min−1; p=0.028). This difference was almost completely accounted for by a reduction in non-oxidative glucose metabolism (17.7±1.9 vs 27.4±2.7 Μmol·kg lean body mass−1. min−1; p = 0.010), which correlated inversely with the AER (r=−0.543; p=0.013). These results suggest that in non-diabetic individuals genetically predisposed to NIDDM, abnormal AER is associated with insulin resistance and abnormalities in glucose and lipid metabolism.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00400643

    Articles: DFG German National Licenses
  6. 6
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Key words Microalbuminuria ; insulin resistance syndrome ; insulin sensitivity ; euglycaemic hyperinsulinaemic clamp.
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Microalbuminuria has recently been associated with insulin resistance in both insulin-dependent and non-insulin-dependent (NIDDM) diabetes mellitus. To establish whether microalbuminuria in non-diabetic subjects as well is associated with insulin resistance and associated abnormalities in glucose and lipid metabolism, oral glucose tolerance tests were performed with measurement of urinary albumin excretion rate, lipids and lipoproteins in 582 male non-diabetic first-degree relatives of patients with NIDDM. In addition, insulin sensitivity was assessed in 20 of these subjects with the euglycaemic hyperinsulinaemic clamp technique. Abnormal albumin excretion rate (AER), defined as AER 15–200 μg/min, was associated with higher systolic blood pressure (p 〈 0.05), higher fasting glucose values (p 〈 0.05), lower HDL-cholesterol (p 〈 0.05) and lower apolipoprotein A-I (p 〈 0.05) concentrations than observed in subjects with normal AER. The rate of glucose metabolism was lower in subjects with abnormal compared to subjects with normal albumin excretion rate (38.0 ± 2.8 vs 47.3 ± 2.4 μmol · kg lean body mass–1· min–1; p = 0.028). This difference was almost completely accounted for by a reduction in non-oxidative glucose metabolism (17.7 ± 1.9 vs 27.4 ± 2.7 μmol · kg lean body mass–1· min–1; p = 0.010), which correlated inversely with the AER (r = –0.543; p = 0.013). These results suggest that in non-diabetic individuals genetically predisposed to NIDDM, abnormal AER is associated with insulin resistance and abnormalities in glucose and lipid metabolism. [Diabetologia (1995) 38: 363 –369]
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00400643

    Articles: DFG German National Licenses
  7. 7
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Keywords Heritability ; albumin excretion rate ; Type II (non-insulin-dependent) diabetes mellitus ; microalbuminuria ; diabetic nephropathy.
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Aims/hypothesis. To study whether albumin excretion rate is an inherited trait in families of patients with Type II (non-insulin-dependent) diabetes mellitus. Methods. We used three different approaches. Heritability of albumin excretion rate was studied in 267 nuclear families from the Botnia Study in Western Finland using parent-offspring regression. Albumin excretion rate was also measured in 206 non-diabetic offspring of 119 Type II diabetic parents with or without albuminuria (albumin excretion rate 〉 20 μg/min). Finally, albumin excretion rate was measured in altogether 652 siblings of 74 microalbuminuric and 320 normoalbuminuric probands. To study the potential confounding effect of blood pressure, the heritability of blood pressure was estimated in 718 nuclear families. Results. Using parent-offspring regression, the heritability of albumin excretion rate was about 30 %, being the strongest from mothers to sons (35–39 % resemblance). The heritability for systolic blood pressure ranged from 10 to 20 % and for diastolic blood pressure from 10 to 27 %. Offspring of albuminuric Type II diabetic parents had higher albumin excretion rates (median 5.4 [range 1.0–195] vs 4.0 [1.0–23] μg/min, p = 0.0001) and a higher frequency of microalbuminuria (11 vs 2 %, p = 0.012) than offspring of normoalbuminuric parents. Further, siblings of microalbuminuric probands had higher albumin excretion rates than siblings of normoalbuminuric probands (4.1 [0.6–14.5] vs 3.6 [0.2–14.4] μg/min, p 〈 0.01). Conclusion/interpretation. The data suggest that albumin excretion rate is an inherited trait in families of patients with Type II diabetes. [Diabetologia (1999) 42: 1359–1366]
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/s001250051450

    Articles: DFG German National Licenses
  8. 8
    Dornan, T. ; Groop, L. C.
    Springer
    Published 1992
    Staff View
    ISSN:
    1432-0428
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00400860

    Articles: DFG German National Licenses
  9. 9
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Keywords Hyperglycaemia ; mass action effect ; glucose-mediated glucose metabolism ; glucose oxidation ; non-oxidative glucose metabolism.
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary The ability of hyperglycaemia to enhance glucose uptake was evaluated in 9 non-insulin-dependent (NIDDM), 7 insulin-dependent (IDDM) diabetic subjects, and in 6 young and 9 older normal volunteers. Following overnight insulin-induced euglycaemia, a sequential three-step hyperglycaemic clamp (+ 2.8 + 5.6, and + 11.2 mmol/l above baseline) was performed with somatostatin plus replacing doses of basal insulin and glucagon, 3-3H-glucose infusion and indirect calorimetry. In the control subjects as a whole, glucose disposal increased at each hyperglycaemic step (13.1 ± 0.6, 15.7 ± 0.7, and 26.3 ± 1.1 μmol/kg · min). In NIDDM (10.5 ± 0.2, 12.1 ± 1.0, and 17.5 ± 1.1 μmol/kg · min), and IDDM (11.2 ± 0.8, 12.9 ± 1.0, and 15.6 ± 1.1 μmol/kg · min) glucose disposal was lower during all three steps (p 〈 0.05–0.005). Hepatic glucose production declined proportionally to plasma glucose concentration to a similar extent in all four groups of patients. In control subjects, hyperglycaemia stimulated glucose oxidation (+ 4.4 ± 0.7 μmol/kg · min) only at + 11.2 mmol/l (p 〈 0.05), while non-oxidative glucose metabolism increased at each hyperglycaemic step (+ 3.1 ± 0.7; + 3.5 ± 0.9, and + 10.8 ± 1.7 μmol/kg · min; all p 〈 0.05). In diabetic patients, no increment in glucose oxidation was elicited even at the highest hyperglycaemic plateau (IDDM = + 0.5 ± 1.5; NIDDM = + 0.2 ± 0.6 μmol/kg · min) and non-oxidative glucose metabolism was hampered (IDDM = + 1.8 ± 1.5, + 3.1 ± 1.7, and + 4.3 ± 1.8; NIDDM = + 0.7 ± 0.6, 2.1 ± 0.9, and + 7.0 ± 0.8 μmol/kg · min; p 〈 0.05–0.005). Blood lactate concentration increased and plasma non-esterified fatty acid (NEFA) fell in control (p 〈 0.05) but not in diabetic subjects. The increments in blood lactate were correlated with the increase in non-oxidative glucose disposal and with the decrease in plasma NEFA. In conclusion: 1) the ability of hyperglycaemia to promote glucose disposal is impaired in NIDDM and IDDM; 2) stimulation of glucose oxidation and non-oxidative glucose metabolism accounts for glucose disposal; 3) both pathways of glucose metabolism are impaired in diabetic patients; 4) impaired ability of hyperglycaemia to suppress plasma NEFA is present in these patients. These results suggest that glucose resistance, that is the ability of glucose itself to promote glucose utilization, is impaired in both IDDM and NIDDM patients. [Diabetologia (1997) 40: 687–697]
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/s001250050735

    Articles: DFG German National Licenses
  10. 10
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Keywords Muscle glycogen synthase gene ; GYS1 ; paired-sibling analysis ; Type II diabetes ; hypertension ; metabolic syndrome ; chromosome 19 ; candidate gene ; myocardial infarction ; microalbuminuria.
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Aims/hypothesis. We have previously shown an association between a XbaI polymorphism in the muscle glycogen synthase gene (GYS1) and both Type II (non–insulin–dependent) diabetes mellitus and hypertension. Association studies are, however, hampered by the selection of the control group. To circumvent these problems we addressed the same question using a novel genotype discordant paired-sibling approach. Methods. We identified 122 sex-matched sib-pairs discordant for the Xba1 polymorphism among a new set of 743 Finnish subjects from 227 families with Type II diabetes and paired analyses were done by McNemar test of symmetry and by permutation tests. Results. Paired analysis showed that siblings with the A2 variant had more hypertension (p = 0.0067), obesity (p = 0.033) and microalbuminuria (p = 0.031) but not significantly more Type II diabetes (p = 0.27) than siblings with the A1 variant. Siblings with the A2 variant were more often treated by insulin (p = 0.050) or anti-hypertensive medication (p = 0.0060) or both. Diabetic A2 variant carriers had higher triglyceride (p = 0.023) and lower HDL cholesterol (p = 0.0059) concentrations and an earlier age at onset of diabetes (p = 0.022) than diabetic siblings with the A1 variant. In non-diabetic sib-pairs the presence of the A2 variant was associated with higher diastolic (p = 0.0014) blood pressure. Finally, the allele frequency of the XbaI polymorphism differed between 216 randomly chosen unrelated Type II diabetic patients and 115 unrelated healthy control spouses without a family history of Type II diabetes (12.7 vs. 6.5 %, p = 0.013). Conclusion/interpretation. The A2 allele of the XbaI polymorphism in the GYS1 confers an increased susceptibility to different features of the metabolic syndrome and Type II diabetes. [Diabetologia (1999) 42: 1138–1145]
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/s001250051282

    Articles: DFG German National Licenses
  11. 11
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Type 2 (non-insulin-dependent) diabetes mellitus ; insulin resistance ; glucose transport ; genes
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary To study whether insulin resistance in Type 2 (non-insulin-dependent) diabetes mellitus is due to a defect in the expression of the insulin-responsive glucose transporter gene (GLUT-4) in human skeletal muscle, we measured the level of GLUT-4 mRNA and (in some of the subjects) its protein in muscle biopsies taken from 14 insulin-resistant patients with Type 2 diabetes, 10 first-degree relatives of the diabetic patients and 12 insulin-sensitive control subjects. Insulin sensitivity was measured with a +45 mU· $${\text{m}}^{{\text{2}}^{{\text{ - 1}}} } $$ ·min−1 euglycaemic insulin clamp in combination with indirect calorimetry and infusion of [3-3H]glucose. GLUT-4 mRNA was measured using a human GLUT-4 cDNA probe and GLUT-4 protein with a polyclonal antibody specific for the 15 amino acid carboxyterminal peptide. Both Type 2 diabetic patients and their relatives showed impaired stimulation of total-body glucose disposal by insulin compared with control subjects (29.5±2.1 and 34.0±4.8 vs 57.9±3.1 μmol·kg lean body mass−1·min−1; p〈0.01). This impairment in glucose disposal was primarily accounted for by a reduction in insulin-stimulated storage of glucose as glycogen (13.0±2.4 and 15.6±3.9 vs 36.9±2.2 μmol·kg lean body mass−1·min−1; p〈0.01). The levels of GLUT-4 mRNA expressed both per μg of total RNA and per μg DNA, were higher in the diabetic patients compared with the control subjects (116±25 vs 53±10 pg/μg RNA and 177±35 vs 112±29 pg/μg DNA; p〈0.05, p〈0.01, respectively). The GLUT-4 mRNA levels in the relatives were not significantly different from that observed in the control subjects (90±16 pg/μg RNA and 117±23 pg/μg DNA; p = NS). The GLUT-4 protein levels did not significantly differ between control subjects, diabetic patients and relatives (494±85, 567±133 and 323±80 cpm/100 μg protein). No correlation was observed between the level of GLUT-4 mRNA andits protein. However, the level of GLUT-4 mRNA and the rate of total-body glucose disposal correlated positively in the control group and in the relatives (both p〈0.05) but not in the diabetic subjects. A positive correlation between the level of GLUT-4 protein and total-body glucose disposal was also observed in the control subjects (r = 0.759; p〈0.05) and in the relatives (r = 0.794; p〈0.01) but not in the diabetic subjects. We conclude that insulin resistance in Type 2 diabetes is not related to a defect in the expression of the GLUT-4 gene in skeletal muscle. Nevertheless, the levels of GLUT-4 mRNA and GLUT-4 protein are related to the rate of total-body glucose disposal in subjects with normal fasting glucose concentrations.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00402546

    Articles: DFG German National Licenses
  12. 12
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Insulin resistance ; glucose transport ; muscle ; insulin ; GLUT-4 ; NIDDM
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary We examined whether insulin resistance, i. e. impaired insulin stimulated glucose uptake in NIDDM patients and their first-degree relatives is associated with alterations in the effect of insulin on the expression of the GLUT-4 gene in skeletal muscle in vivo. Levels of GLUT-4 mRNA and protein were measured in muscle biopsies taken before and after a euglycaemic insulin clamp from 14 NIDDM patients, 13 of their first-degree relatives and 17 control subjects. Insulin stimulated glucose uptake was decreased in the diabetic subjects (19.8±3.0 μmol · kg LBM−1 · min−1, both p〈0.001) compared with control subjects (44.1±2.5 μmol · kg LBM−1 · min−1) and relatives (39.9±3.3 μmol · kg LBM−1 · min−1). Basal GLUT-4 mRNA levels were significantly higher in diabetic subjects and relatives compared to control subjects (99±8 and 108±9 pg/μg RNA vs 68±5 pg/μg RNA; both p〈0.01). Insulin increased GLUT-4 mRNA levels in all control subjects (from 68±5 to 92±6 pg/ug RNA; p〈0.0001), but not in the diabetic patients (from 99±8 to 90±8 pg/μg RNA, NS), or their relatives (from 94±9 to 101±11 pg/μg RNA, NS). In the relatives, individual basal GLUT-4 mRNA concentrations varied between 55 and 137 pg/μg RNA. Insulin-resistant (n=6, mean glucose uptake rate=30.6±3.4 μmol · kg LBM−1 · min−1) but not insulin-sensitive relatives (n=7, mean glucose uptake rate=47.4±3.2 μmol · kg LBM−1 · min−1) had higher basal GLUT-4 mRNA concentrations compared to control subjects (108±9 vs 68±5 pg/ug RNA, p〈0.01). GLUT-4 protein content in muscle did not differ between the groups in the basal state and remained unchanged in all groups after insulin infusion. Neither insulin-stimulated GLUT-4 mRNA nor protein concentrations correlated with insulin-stimulated glucose uptake in any of the groups studied. We conclude, that impaired glucose uptake in NIDDM is not related to insulin-stimulated GLUT-4 mRNA or protein concentrations. Acute stimulation of GLUT-4 mRNA by insulin is altered in skeletal muscle of NIDDM patients and their first-degree relatives. This might be a consequence of chronic hyperinsulinaemia elevating basal GLUT-4 mRNA concentrations rather than the cause of insulin resistance.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00408478

    Articles: DFG German National Licenses
  13. 13
    Groop, L. C. ; Widén, E. ; Ferrannini, E.
    Springer
    Published 1993
    Staff View
    ISSN:
    1432-0428
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00400814

    Articles: DFG German National Licenses
  14. 14
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Type 1 (insulin-dependent) diabetes mellitus ; Type 2 (non-insulin-dependent) diabetes ; islet cell antibodies ; glucose metabolism
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary It is still a matter of debate whether patients who develop islet-cell antibody positive autoimmune diabetes during adulthood represent slowly evolving Type 1 (insulindependent) diabetes mellitus or a separate subgroup of Type 2 (non-insulin-dependent) diabetes. To address this question, we measured C-peptide response to a test meal, and energy metabolism in the basal state and during a euglycaemic, hyperinsulinaemic clamp in (1) 29 patients with Type 2 diabetes; (2) 10 patients with autoimmune diabetes developing after the age of 40 years; (3) 11 patients with Type 1 diabetes and (4) 15 non-diabetic control subjects. While C-peptide response to a test meal was lacking in Type 1 diabetes and nearly normal in Type 2 diabetes, the C-peptide response in autoimmune diabetes was markedly reduced. Patients with Type 2 diabetes, autoimmune diabetes and Type 1 diabetes showed a 47%, 45% and 42%, respectively, reduction in the rate of non-oxidative glucose metabolism compared with control subjects (p〈0.05-0.01). Similarly, patients with Type 2 diabetes (+52%), autoimmune diabetes (+27%) and Type 1 diabetes (+33%) presented with an enhanced basal rate of hepatic glucose production, which was less suppressed by insulin compared with healthy control subjects (p〈0.01). However, patients with autoimmune diabetes derived more energy from oxidation of glucose and proteins and less energy from oxidation of lipids than patients with either Type 1 or Type 2 diabetes (p〈0.05-0.01). In conclusion, patients who develop autoimmune diabetes during adulthood share the defects in hepatic glucose production and in non-oxidative glucose metabolism with both Type 1 and Type 2 diabetes. Oxidative energy metabolism in autoimmune diabetes, however, differs from that observed in Type 1 and Type 2 diabetes. Given the metabolic characteristics of these patients, it seems justified to consider autoimmune diabetes in adults as a subgroup of diabetes developing in adult age.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00404024

    Articles: DFG German National Licenses
  15. 15
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Key words Insulin resistance, glucose transport, muscle, insulin, GLUT-4, NIDDM.
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary We examined whether insulin resistance, i. e. impaired insulin stimulated glucose uptake in NIDDM patients and their first-degree relatives is associated with alterations in the effect of insulin on the expression of the GLUT-4 gene in skeletal muscle in vivo. Levels of GLUT-4 mRNA and protein were measured in muscle biopsies taken before and after a euglycaemic insulin clamp from 14 NIDDM patients, 13 of their first-degree relatives and 17 control subjects. Insulin stimulated glucose uptake was decreased in the diabetic subjects (19.8±3.0 µmol·kg LBM–1·min–1, both p〈0.001) compared with control subjects (44.1±2.5 µmol·kg LBM–1·min–1) and relatives (39.9±3.3 µmol·kg LBM–1·min–1). Basal GLUT-4 mRNA levels were significantly higher in diabetic subjects and relatives compared to control subjects (99±8 and 108±9 pg/µg RNA vs 68±5 pg/µg RNA; both p〈0.01). Insulin increased GLUT-4 mRNA levels in all control subjects (from 68±5 to 92±6 pg/µg RNA; p〈0.0001), but not in the diabetic patients (from 99±8 to 90±8 pg/µg RNA, NS), or their relatives (from 94±9 to 101±11 pg/µg RNA, NS). In the relatives, individual basal GLUT-4 mRNA concentrations varied between 55 and 137 pg/µg RNA. Insulin-resistant (n =6, mean glucose uptake rate =30.6±3.4 µmol·kg LBM–1·min–1) but not insulin-sensitive relatives (n =7, mean glucose uptake rate =47.4±3.2 µmol·kg LBM–1·min–1) had higher basal GLUT-4 mRNA concentrations compared to control subjects (108±9 vs 68±5 pg/µg RNA, p〈0.01). GLUT-4 protein content in muscle did not differ between the groups in the basal state and remained unchanged in all groups after insulin infusion. Neither insulin-stimulated GLUT-4 mRNA nor protein concentrations correlated with insulin-stimulated glucose uptake in any of the groups studied. We conclude, that impaired glucose uptake in NIDDM is not related to insulin-stimulated GLUT-4 mRNA or protein concentrations. Acute stimulation of GLUT-4 mRNA by insulin is altered in skeletal muscle of NIDDM patients and their first-degree relatives. This might be a consequence of chronic hyperinsulinaemia elevating basal GLUT-4 mRNA concentrations rather than the cause of insulin resistance. [Diabetologia (1994) 37: 401–407]
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00408478

    Articles: DFG German National Licenses
  16. 16
    Staff View
    ISSN:
    1432-5233
    Keywords:
    Insulin ; C-peptide ; Glucose ; Glipizide ; Non-insulin-dependent diabetes mellitus
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract The effect of a rapid-acting sulphonylurea, glipizide, on the dose-response relationship between the β-cell response (insulin and C-peptide secretion) and the ambient plasma glucose concentration was examined in 12 healthy and 6 non-insulin-dependent diabetic subjects. The subjects participated in two sets of experiments which were performed in random order: (A) four hyperglycaemic clamp studies, during which the plasma glucose concentration was raised for 120 min by 1 (only in healthy subjects), 3, 7, and 17 mmol/l; and (B) the same four hyperglycaemic clamp studies preceded by ingestion of 5 mg glipizide. All subjects participated in a further study, in which glipizide was ingested and the plasma glucose concentration was maintained at the basal level. In control subjects in the absence of glipizide, the firstphase plasma insulin response (0–10 min) increased progressively with increasing plasma glucose concentration up to 10 mmol/l, above which it tended to plateau. Glipizide augmented the first-phase insulin response without changing the slope of the regression line relating plasma insulin to glucose concentrations. The second-phase plasma insulin response (20–120 min) increased linearly with increasing hyperglycaemia (r=0.997). Glipizide alone increased the plasma insulin response by 180 pmol/l. A similar increase in plasma insulin response following glipizide was observed at each hyperglycaemic step, indicating that glipizide did not affect the sensitivity of the β-cell to glucose. First-phase insulin secretion was reduced in the type 2 (non-insulin-dependent) diabetic patients, and was not influenced by glipizide. The dose-response curve relating second-phase insulin secretion to the ambient plasma glucose concentration was significantly (P〈0.001) flatter in the diabetic patients than in the control subjects. Glipizide alone increased the plasma insulin response by 60 pmol/l without changing the slope of the dose-response curve. It is concluded that, in both type 2 diabetic patients and healthy subjects: (A) sulphonylurea augments glucose-stimulated second-phase insulin secretion without changing the sensitivity of the β-cell to glucose; (B) first-phase insulin secretion is reduced in non-insulin-dependent diabetic patients with fasting hyperglycaemia and is not influenced by sulphonylurea.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00579720

    Articles: DFG German National Licenses