Search Results - (Author, Cooperation:M. Nauck)

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  1. 1
    D. P. Hibar ; J. L. Stein ; M. E. Renteria ; A. Arias-Vasquez ; S. Desrivieres ; N. Jahanshad ; R. Toro ; K. Wittfeld ; L. Abramovic ; M. Andersson ; B. S. Aribisala ; N. J. Armstrong ; M. Bernard ; M. M. Bohlken ; M. P. Boks ; J. Bralten ; A. A. Brown ; M. M. Chakravarty ; Q. Chen ; C. R. Ching ; G. Cuellar-Partida ; A. den Braber ; S. Giddaluru ; A. L. Goldman ; O. Grimm ; T. Guadalupe ; J. Hass ; G. Woldehawariat ; A. J. Holmes ; M. Hoogman ; D. Janowitz ; T. Jia ; S. Kim ; M. Klein ; B. Kraemer ; P. H. Lee ; L. M. Olde Loohuis ; M. Luciano ; C. Macare ; K. A. Mather ; M. Mattheisen ; Y. Milaneschi ; K. Nho ; M. Papmeyer ; A. Ramasamy ; S. L. Risacher ; R. Roiz-Santianez ; E. J. Rose ; A. Salami ; P. G. Samann ; L. Schmaal ; A. J. Schork ; J. Shin ; L. T. Strike ; A. Teumer ; M. M. van Donkelaar ; K. R. van Eijk ; R. K. Walters ; L. T. Westlye ; C. D. Whelan ; A. M. Winkler ; M. P. Zwiers ; S. Alhusaini ; L. Athanasiu ; S. Ehrlich ; M. M. Hakobjan ; C. B. Hartberg ; U. K. Haukvik ; A. J. Heister ; D. Hoehn ; D. Kasperaviciute ; D. C. Liewald ; L. M. Lopez ; R. R. Makkinje ; M. Matarin ; M. A. Naber ; D. R. McKay ; M. Needham ; A. C. Nugent ; B. Putz ; N. A. Royle ; L. Shen ; E. Sprooten ; D. Trabzuni ; S. S. van der Marel ; K. J. van Hulzen ; E. Walton ; C. Wolf ; L. Almasy ; D. Ames ; S. Arepalli ; A. A. Assareh ; M. E. Bastin ; H. Brodaty ; K. B. Bulayeva ; M. A. Carless ; S. Cichon ; A. Corvin ; J. E. Curran ; M. Czisch ; G. I. de Zubicaray ; A. Dillman ; R. Duggirala ; T. D. Dyer ; S. Erk ; I. O. Fedko ; L. Ferrucci ; T. M. Foroud ; P. T. Fox ; M. Fukunaga ; J. R. Gibbs ; H. H. Goring ; R. C. Green ; S. Guelfi ; N. K. Hansell ; C. A. Hartman ; K. Hegenscheid ; A. Heinz ; D. G. Hernandez ; D. J. Heslenfeld ; P. J. Hoekstra ; F. Holsboer ; G. Homuth ; J. J. Hottenga ; M. Ikeda ; C. R. Jack, Jr. ; M. Jenkinson ; R. Johnson ; R. Kanai ; M. Keil ; J. W. Kent, Jr. ; P. Kochunov ; J. B. Kwok ; S. M. Lawrie ; X. Liu ; D. L. Longo ; K. L. McMahon ; E. Meisenzahl ; I. Melle ; S. Mohnke ; G. W. Montgomery ; J. C. Mostert ; T. W. Muhleisen ; M. A. Nalls ; T. E. Nichols ; L. G. Nilsson ; M. M. Nothen ; K. Ohi ; R. L. Olvera ; R. Perez-Iglesias ; G. B. Pike ; S. G. Potkin ; I. Reinvang ; S. Reppermund ; M. Rietschel ; N. Romanczuk-Seiferth ; G. D. Rosen ; D. Rujescu ; K. Schnell ; P. R. Schofield ; C. Smith ; V. M. Steen ; J. E. Sussmann ; A. Thalamuthu ; A. W. Toga ; B. J. Traynor ; J. Troncoso ; J. A. Turner ; M. C. Valdes Hernandez ; D. van 't Ent ; M. van der Brug ; N. J. van der Wee ; M. J. van Tol ; D. J. Veltman ; T. H. Wassink ; E. Westman ; R. H. Zielke ; A. B. Zonderman ; D. G. Ashbrook ; R. Hager ; L. Lu ; F. J. McMahon ; D. W. Morris ; R. W. Williams ; H. G. Brunner ; R. L. Buckner ; J. K. Buitelaar ; W. Cahn ; V. D. Calhoun ; G. L. Cavalleri ; B. Crespo-Facorro ; A. M. Dale ; G. E. Davies ; N. Delanty ; C. Depondt ; S. Djurovic ; W. C. Drevets ; T. Espeseth ; R. L. Gollub ; B. C. Ho ; W. Hoffmann ; N. Hosten ; R. S. Kahn ; S. Le Hellard ; A. Meyer-Lindenberg ; B. Muller-Myhsok ; M. Nauck ; L. Nyberg ; M. Pandolfo ; B. W. Penninx ; J. L. Roffman ; S. M. Sisodiya ; J. W. Smoller ; H. van Bokhoven ; N. E. van Haren ; H. Volzke ; H. Walter ; M. W. Weiner ; W. Wen ; T. White ; I. Agartz ; O. A. Andreassen ; J. Blangero ; D. I. Boomsma ; R. M. Brouwer ; D. M. Cannon ; M. R. Cookson ; E. J. de Geus ; I. J. Deary ; G. Donohoe ; G. Fernandez ; S. E. Fisher ; C. Francks ; D. C. Glahn ; H. J. Grabe ; O. Gruber ; J. Hardy ; R. Hashimoto ; H. E. Hulshoff Pol ; E. G. Jonsson ; I. Kloszewska ; S. Lovestone ; V. S. Mattay ; P. Mecocci ; C. McDonald ; A. M. McIntosh ; R. A. Ophoff ; T. Paus ; Z. Pausova ; M. Ryten ; P. S. Sachdev ; A. J. Saykin ; A. Simmons ; A. Singleton ; H. Soininen ; J. M. Wardlaw ; M. E. Weale ; D. R. Weinberger ; H. H. Adams ; L. J. Launer ; S. Seiler ; R. Schmidt ; G. Chauhan ; C. L. Satizabal ; J. T. Becker ; L. Yanek ; S. J. van der Lee ; M. Ebling ; B. Fischl ; W. T. Longstreth, Jr. ; D. Greve ; H. Schmidt ; P. Nyquist ; L. N. Vinke ; C. M. van Duijn ; L. Xue ; B. Mazoyer ; J. C. Bis ; V. Gudnason ; S. Seshadri ; M. A. Ikram ; N. G. Martin ; M. J. Wright ; G. Schumann ; B. Franke ; P. M. Thompson ; S. E. Medland
    Nature Publishing Group (NPG)
    Published 2015
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    Publication Date:
    2015-01-22
    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:
    Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/genetics ; Apoptosis/genetics ; Brain/*anatomy & histology ; Caudate Nucleus/anatomy & histology ; Child ; Female ; Gene Expression Regulation, Developmental/genetics ; Genetic Loci/genetics ; Genetic Variation/*genetics ; *Genome-Wide Association Study ; Hippocampus/anatomy & histology ; Humans ; Magnetic Resonance Imaging ; Male ; Membrane Proteins/genetics ; Middle Aged ; Organ Size/genetics ; Putamen/anatomy & histology ; Sex Characteristics ; Skull/anatomy & histology ; Young Adult
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  2. 2
    C. Gieger ; A. Radhakrishnan ; A. Cvejic ; W. Tang ; E. Porcu ; G. Pistis ; J. Serbanovic-Canic ; U. Elling ; A. H. Goodall ; Y. Labrune ; L. M. Lopez ; R. Magi ; S. Meacham ; Y. Okada ; N. Pirastu ; R. Sorice ; A. Teumer ; K. Voss ; W. Zhang ; R. Ramirez-Solis ; J. C. Bis ; D. Ellinghaus ; M. Gogele ; J. J. Hottenga ; C. Langenberg ; P. Kovacs ; P. F. O'Reilly ; S. Y. Shin ; T. Esko ; J. Hartiala ; S. Kanoni ; F. Murgia ; A. Parsa ; J. Stephens ; P. van der Harst ; C. Ellen van der Schoot ; H. Allayee ; A. Attwood ; B. Balkau ; F. Bastardot ; S. Basu ; S. E. Baumeister ; G. Biino ; L. Bomba ; A. Bonnefond ; F. Cambien ; J. C. Chambers ; F. Cucca ; P. D'Adamo ; G. Davies ; R. A. de Boer ; E. J. de Geus ; A. Doring ; P. Elliott ; J. Erdmann ; D. M. Evans ; M. Falchi ; W. Feng ; A. R. Folsom ; I. H. Frazer ; Q. D. Gibson ; N. L. Glazer ; C. Hammond ; A. L. Hartikainen ; S. R. Heckbert ; C. Hengstenberg ; M. Hersch ; T. Illig ; R. J. Loos ; J. Jolley ; K. T. Khaw ; B. Kuhnel ; M. C. Kyrtsonis ; V. Lagou ; H. Lloyd-Jones ; T. Lumley ; M. Mangino ; A. Maschio ; I. Mateo Leach ; B. McKnight ; Y. Memari ; B. D. Mitchell ; G. W. Montgomery ; Y. Nakamura ; M. Nauck ; G. Navis ; U. Nothlings ; I. M. Nolte ; D. J. Porteous ; A. Pouta ; P. P. Pramstaller ; J. Pullat ; S. M. Ring ; J. I. Rotter ; D. Ruggiero ; A. Ruokonen ; C. Sala ; N. J. Samani ; J. Sambrook ; D. Schlessinger ; S. Schreiber ; H. Schunkert ; J. Scott ; N. L. Smith ; H. Snieder ; J. M. Starr ; M. Stumvoll ; A. Takahashi ; W. H. Tang ; K. Taylor ; A. Tenesa ; S. Lay Thein ; A. Tonjes ; M. Uda ; S. Ulivi ; D. J. van Veldhuisen ; P. M. Visscher ; U. Volker ; H. E. Wichmann ; K. L. Wiggins ; G. Willemsen ; T. P. Yang ; J. Hua Zhao ; P. Zitting ; J. R. Bradley ; G. V. Dedoussis ; P. Gasparini ; S. L. Hazen ; A. Metspalu ; M. Pirastu ; A. R. Shuldiner ; L. Joost van Pelt ; J. J. Zwaginga ; D. I. Boomsma ; I. J. Deary ; A. Franke ; P. Froguel ; S. K. Ganesh ; M. R. Jarvelin ; N. G. Martin ; C. Meisinger ; B. M. Psaty ; T. D. Spector ; N. J. Wareham ; J. W. Akkerman ; M. Ciullo ; P. Deloukas ; A. Greinacher ; S. Jupe ; N. Kamatani ; J. Khadake ; J. S. Kooner ; J. Penninger ; I. Prokopenko ; D. Stemple ; D. Toniolo ; L. Wernisch ; S. Sanna ; A. A. Hicks ; A. Rendon ; M. A. Ferreira ; W. H. Ouwehand ; N. Soranzo
    Nature Publishing Group (NPG)
    Published 2011
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    Publication Date:
    2011-12-06
    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:
    Animals ; Blood Platelets/*cytology/metabolism ; Cell Size ; Drosophila Proteins/genetics ; Drosophila melanogaster/genetics ; Europe ; Gene Expression Profiling ; Gene Silencing ; Genome, Human/genetics ; Genome-Wide Association Study ; Hematopoiesis/*genetics ; Humans ; Megakaryocytes/*cytology/metabolism ; Platelet Count ; Protein Interaction Maps ; Transcription, Genetic/genetics ; Zebrafish/genetics ; Zebrafish Proteins/genetics
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  3. 3
    S. Jacquemont ; A. Reymond ; F. Zufferey ; L. Harewood ; R. G. Walters ; Z. Kutalik ; D. Martinet ; Y. Shen ; A. Valsesia ; N. D. Beckmann ; G. Thorleifsson ; M. Belfiore ; S. Bouquillon ; D. Campion ; N. de Leeuw ; B. B. de Vries ; T. Esko ; B. A. Fernandez ; F. Fernandez-Aranda ; J. M. Fernandez-Real ; M. Gratacos ; A. Guilmatre ; J. Hoyer ; M. R. Jarvelin ; R. F. Kooy ; A. Kurg ; C. Le Caignec ; K. Mannik ; O. S. Platt ; D. Sanlaville ; M. M. Van Haelst ; S. Villatoro Gomez ; F. Walha ; B. L. Wu ; Y. Yu ; A. Aboura ; M. C. Addor ; Y. Alembik ; S. E. Antonarakis ; B. Arveiler ; M. Barth ; N. Bednarek ; F. Bena ; S. Bergmann ; M. Beri ; L. Bernardini ; B. Blaumeiser ; D. Bonneau ; A. Bottani ; O. Boute ; H. G. Brunner ; D. Cailley ; P. Callier ; J. Chiesa ; J. Chrast ; L. Coin ; C. Coutton ; J. M. Cuisset ; J. C. Cuvellier ; A. David ; B. de Freminville ; B. Delobel ; M. A. Delrue ; B. Demeer ; D. Descamps ; G. Didelot ; K. Dieterich ; V. Disciglio ; M. Doco-Fenzy ; S. Drunat ; B. Duban-Bedu ; C. Dubourg ; J. S. El-Sayed Moustafa ; P. Elliott ; B. H. Faas ; L. Faivre ; A. Faudet ; F. Fellmann ; A. Ferrarini ; R. Fisher ; E. Flori ; L. Forer ; D. Gaillard ; M. Gerard ; C. Gieger ; S. Gimelli ; G. Gimelli ; H. J. Grabe ; A. Guichet ; O. Guillin ; A. L. Hartikainen ; D. Heron ; L. Hippolyte ; M. Holder ; G. Homuth ; B. Isidor ; S. Jaillard ; Z. Jaros ; S. Jimenez-Murcia ; G. J. Helas ; P. Jonveaux ; S. Kaksonen ; B. Keren ; A. Kloss-Brandstatter ; N. V. Knoers ; D. A. Koolen ; P. M. Kroisel ; F. Kronenberg ; A. Labalme ; E. Landais ; E. Lapi ; V. Layet ; S. Legallic ; B. Leheup ; B. Leube ; S. Lewis ; J. Lucas ; K. D. MacDermot ; P. Magnusson ; C. Marshall ; M. Mathieu-Dramard ; M. I. McCarthy ; T. Meitinger ; M. A. Mencarelli ; G. Merla ; A. Moerman ; V. Mooser ; F. Morice-Picard ; M. Mucciolo ; M. Nauck ; N. C. Ndiaye ; A. Nordgren ; L. Pasquier ; F. Petit ; R. Pfundt ; G. Plessis ; E. Rajcan-Separovic ; G. P. Ramelli ; A. Rauch ; R. Ravazzolo ; A. Reis ; A. Renieri ; C. Richart ; J. S. Ried ; C. Rieubland ; W. Roberts ; K. M. Roetzer ; C. Rooryck ; M. Rossi ; E. Saemundsen ; V. Satre ; C. Schurmann ; E. Sigurdsson ; D. J. Stavropoulos ; H. Stefansson ; C. Tengstrom ; U. Thorsteinsdottir ; F. J. Tinahones ; R. Touraine ; L. Vallee ; E. van Binsbergen ; N. Van der Aa ; C. Vincent-Delorme ; S. Visvikis-Siest ; P. Vollenweider ; H. Volzke ; A. T. Vulto-van Silfhout ; G. Waeber ; C. Wallgren-Pettersson ; R. M. Witwicki ; S. Zwolinksi ; J. Andrieux ; X. Estivill ; J. F. Gusella ; O. Gustafsson ; A. Metspalu ; S. W. Scherer ; K. Stefansson ; A. I. Blakemore ; J. S. Beckmann ; P. Froguel
    Nature Publishing Group (NPG)
    Published 2011
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    Publication Date:
    2011-09-02
    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:
    Adolescent ; Adult ; Aged ; Aging ; Body Height/genetics ; *Body Mass Index ; Case-Control Studies ; Child ; Child, Preschool ; Chromosomes, Human, Pair 16/*genetics ; Cohort Studies ; Comparative Genomic Hybridization ; Developmental Disabilities/genetics ; Energy Metabolism/genetics ; Europe ; Female ; Gene Dosage/*genetics ; Gene Duplication/genetics ; Gene Expression Profiling ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Head/anatomy & histology ; Heterozygote ; Humans ; Infant ; Infant, Newborn ; Male ; Mental Disorders/genetics ; Middle Aged ; Mutation/genetics ; North America ; Obesity/*genetics ; *Phenotype ; RNA, Messenger/analysis/genetics ; Sequence Deletion/genetics ; Thinness/*genetics ; Transcription, Genetic ; Young Adult
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  4. 4
    P. van der Harst ; W. Zhang ; I. Mateo Leach ; A. Rendon ; N. Verweij ; J. Sehmi ; D. S. Paul ; U. Elling ; H. Allayee ; X. Li ; A. Radhakrishnan ; S. T. Tan ; K. Voss ; C. X. Weichenberger ; C. A. Albers ; A. Al-Hussani ; F. W. Asselbergs ; M. Ciullo ; F. Danjou ; C. Dina ; T. Esko ; D. M. Evans ; L. Franke ; M. Gogele ; J. Hartiala ; M. Hersch ; H. Holm ; J. J. Hottenga ; S. Kanoni ; M. E. Kleber ; V. Lagou ; C. Langenberg ; L. M. Lopez ; L. P. Lyytikainen ; O. Melander ; F. Murgia ; I. M. Nolte ; P. F. O'Reilly ; S. Padmanabhan ; A. Parsa ; N. Pirastu ; E. Porcu ; L. Portas ; I. Prokopenko ; J. S. Ried ; S. Y. Shin ; C. S. Tang ; A. Teumer ; M. Traglia ; S. Ulivi ; H. J. Westra ; J. Yang ; J. H. Zhao ; F. Anni ; A. Abdellaoui ; A. Attwood ; B. Balkau ; S. Bandinelli ; F. Bastardot ; B. Benyamin ; B. O. Boehm ; W. O. Cookson ; D. Das ; P. I. de Bakker ; R. A. de Boer ; E. J. de Geus ; M. H. de Moor ; M. Dimitriou ; F. S. Domingues ; A. Doring ; G. Engstrom ; G. I. Eyjolfsson ; L. Ferrucci ; K. Fischer ; R. Galanello ; S. F. Garner ; B. Genser ; Q. D. Gibson ; G. Girotto ; D. F. Gudbjartsson ; S. E. Harris ; A. L. Hartikainen ; C. E. Hastie ; B. Hedblad ; T. Illig ; J. Jolley ; M. Kahonen ; I. P. Kema ; J. P. Kemp ; L. Liang ; H. Lloyd-Jones ; R. J. Loos ; S. Meacham ; S. E. Medland ; C. Meisinger ; Y. Memari ; E. Mihailov ; K. Miller ; M. F. Moffatt ; M. Nauck ; M. Novatchkova ; T. Nutile ; I. Olafsson ; P. T. Onundarson ; D. Parracciani ; B. W. Penninx ; L. Perseu ; A. Piga ; G. Pistis ; A. Pouta ; U. Puc ; O. Raitakari ; S. M. Ring ; A. Robino ; D. Ruggiero ; A. Ruokonen ; A. Saint-Pierre ; C. Sala ; A. Salumets ; J. Sambrook ; H. Schepers ; C. O. Schmidt ; H. H. Sillje ; R. Sladek ; J. H. Smit ; J. M. Starr ; J. Stephens ; P. Sulem ; T. Tanaka ; U. Thorsteinsdottir ; V. Tragante ; W. H. van Gilst ; L. J. van Pelt ; D. J. van Veldhuisen ; U. Volker ; J. B. Whitfield ; G. Willemsen ; B. R. Winkelmann ; G. Wirnsberger ; A. Algra ; F. Cucca ; A. P. d'Adamo ; J. Danesh ; I. J. Deary ; A. F. Dominiczak ; P. Elliott ; P. Fortina ; P. Froguel ; P. Gasparini ; A. Greinacher ; S. L. Hazen ; M. R. Jarvelin ; K. T. Khaw ; T. Lehtimaki ; W. Maerz ; N. G. Martin ; A. Metspalu ; B. D. Mitchell ; G. W. Montgomery ; C. Moore ; G. Navis ; M. Pirastu ; P. P. Pramstaller ; R. Ramirez-Solis ; E. Schadt ; J. Scott ; A. R. Shuldiner ; G. D. Smith ; J. G. Smith ; H. Snieder ; R. Sorice ; T. D. Spector ; K. Stefansson ; M. Stumvoll ; W. H. Tang ; D. Toniolo ; A. Tonjes ; P. M. Visscher ; P. Vollenweider ; N. J. Wareham ; B. H. Wolffenbuttel ; D. I. Boomsma ; J. S. Beckmann ; G. V. Dedoussis ; P. Deloukas ; M. A. Ferreira ; S. Sanna ; M. Uda ; A. A. Hicks ; J. M. Penninger ; C. Gieger ; J. S. Kooner ; W. H. Ouwehand ; N. Soranzo ; J. C. Chambers
    Nature Publishing Group (NPG)
    Published 2012
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    Publication Date:
    2012-12-12
    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:
    Animals ; Cell Cycle/genetics ; Cytokines/metabolism ; Drosophila melanogaster/genetics ; Erythrocytes/cytology/*metabolism ; Female ; Gene Expression Regulation/genetics ; *Genetic Loci ; *Genome-Wide Association Study ; Hematopoiesis/genetics ; Hemoglobins/genetics ; Humans ; Male ; Mice ; Organ Specificity ; *Phenotype ; Polymorphism, Single Nucleotide/genetics ; RNA Interference ; Signal Transduction/genetics
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  5. 5
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    ISSN:
    1432-1440
    Keywords:
    Pancreas transplantation ; Insulin secretion ; Pancreatic hormones ; Gastrointestinal peptide hormones ; Rènal elimination (clearance) ; Systemic venous pancreas drainage
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary The secretion of pancreatic and gastrointestinal hormones in the basal state and after nutrient stimuli (50 g glucose, 50 g protein, or 30 g triglyceride administered on separate occasions) was assessed in ten previously type-1-diabetic patients after successful combined kidney and pancreas transplantation (systemic venous drainage). Fasting values were compared to matched non-diabetic kidney-transplanted patients and related to kidney function (endogenous creatinine clearance) and to the type and dosage of immunosuppressive medication. In the fasting state, only IR insulin concentrations were higher in pancreas-kidney-transplanted patients (by 88%; P=0.001) than in the kidney graft recipients. There were significant inverse correlations of plasma C-peptide, GIP, and gastrin immunoreactivity to endogenous creatinine clearance (kidney function). In response to nutrients, insulin secretion (IR insulin, C-peptide) was significantly stimulated by glucose, and — to a lesser degree — also by protein. Pancreatic glucagon was suppressed by glucose and stimulated by protein ingestion. GIP was raised after glucose and triglyceride more than after protein (P=0.0003). GLP-1 immunoreactivity was stimulated by all nutrients, with a tendency towards higher responses to protein and fat (P=0.06). Gastrin was mainly raised by protein. In conclusion, the overall pattern of pancreatic and gastrointestinal hormone release is normal in patients after combined pancreas-kidney-transplantation, but there are some peculiarities due to (a) systemic venous drainage of the pancreas graft (elevated fasting IR insulin) and (b) impaired kidney function (negative correlation of fasting plasma values to endogenous creatinine clearance for C-peptide, GIP, and gastrin). The plasma levels of these important regulatory peptides and their responses to nutrient stimulation are compatible with and may contribute to the well-preserved endocrine function of the pancreatic grafts (normal or slightly impaired glucose tolerance, preserved incretin effect).
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00422937

    Articles: DFG German National Licenses
  6. 6
    Staff View
    ISSN:
    1432-1440
    Keywords:
    Polycythemia vera ; Cytapheresis ; Erythrocytapheresis ; Therapy
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Excess red blood cells (RBC) in patients with polycythemia vera (PV) are usually removed by repeated phlebotomy. In order to improve the efficacy of this treatment, we used isovolemic large-volume erythrocytapheresis (EA) by a cell separator. A retrospective analysis of our experience with 69 PV patients (206 EA procedures) is reported. EA induced a rapid, well-tolerated, and long-lasting reduction of Hct, Hb, and RBC counts, as well as an immediate disappearance or reduction of clinical symptoms of PV, while tissue oxygen tension — as measured in 8 patients — increased. Hct was reduced by EA from 56.8% ±5.6% to 41.9% ±6.6%, Hb from 17.5±2.3 to 12.7±2.4 g%, RBC counts from 7.±0.9 to 5.4±0.9×106/mm3. The mean volume of the apherisate was 1410±418 ml, (mean Hct 79.7%±9.3%), and the actual RBC volume removed 1113±367 ml. The isovolemic procedure was well tolerated and the acceptance by patients seemed to be better than with repeated phlebotomy. In 21 patients whose Hct values (Hct before and after EA 58%±5.7% and 41.5%±4.9%) were regularly followed after EA the mean period with Hct〈50% after a single EA procedure was 6.1±4.1 months (median, 6); in 14 out of these 21 patients a Hct of 〈43% after EA was reached and their mean period with Hct〈50% after EA was 7.6±4.0 months (median, 7.5). For three patients this period was 11, 13, and 15 months, respectively. In our experience large-volume isovolemic EA is a feasible, very effective, and welltolerated alternative treatment modality for PV patients. It may be superior to repeated phlebotomy, especially for patients with excessively increased RBC mass. Only a controlled prospective trial can answer the question, whether EA, due to its rapid effect and due to the long-lasting lower RBC mass, leads to a lower rate of thromboembolic events, and whether EA may delay the necessity for treatment of PV by cytotoxic drugs or P32.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF01648884

    Articles: DFG German National Licenses
  7. 7
    Staff View
    ISSN:
    1433-8580
    Keywords:
    Pancreas denervation ; Pancreas transplantation ; Insulin secretion ; Gastric inhibitory polypeptide ; GIP ; Incretin effect
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Plasma insulin responses to intragastric (i.g.) (1.5 g/kg b.wt.) and “isoglycemic” intravenous (i.v.) glucose were measured in ten unanesthetized young pigs to assess the contribution of gastrointestinal factors to the total insulin secretion as observed after i.g. glucose. The participation of nerves was estimated by comparing metabolic tests performed before and after total surgical pancreatic denervation. In the five animals which survived the procedure, 52.6% of the insulin response after i.g. glucose was calculated to be due to incretion factors, a value similar to the 54.8% found in the preoperative series (with intact pancreatic innervation). The response of IR-GIP to i.g. glucose was not significantly different between preoperative and postoperative tests, although a subtotal duodenectomy had to be performed in the course of the operation designed to completely denervate the pancreas. Intragastric and i.v. (also tested by bolus glucose injection) glucose tolerance was almost identical before and after the operation. It was concluded that nerves do not seem to play a major role in mediating the incretin effect in pigs. Hormonal factors, including GIP, appear to be more important.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF01851954

    Articles: DFG German National Licenses
  8. 8
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Enteroinsular axis ; incretin effect ; cholecystokinin ; gastric inhibitory polypeptide ; insulin secretion ; phenylalanine ; amino acids
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Intraduodenal phenylalanine administration (333 mg/min over 60 min) released endogenous cholecystokinin in healthy young subjects as demonstrated radioimmunologically and by intraduodenal bilirubin and pancreatic enzyme output. Concomitantly, there was only a small increase over basal in circulating immunoreactive-insulin and immunoreactive-C-peptide concentrations. In healthy volunteers intraduodenal infusions of saline (10 ml/min), glucose (333 mg/min) or phenylalanine (333 mg/min) were performed for 60 min when plasma glucose was clamped at approximately 8 mmol/l. Phenylalanine enhanced immunoreactive-insulin and immunoreactive-C-peptide responses three-fold more than did the same amount of glucose. Immuno-reactive gastric inhibitory polypeptide responses were small and not different after glucose and phenylalanine administration. Immunoreactive cholecystokinin was significantly stimulated to 9.4±1.4pmol/l only by intraduodenal phenylalanine. Plasma phenylalanine concentrations increased into the supraphysiological range (approximately 1.5 mmol/l). Intravenous infusions of phenylalanine achieving plasma concentrations of 1.2 mmol/l stimulated insulin secretion at elevated plasma glucose concentrations (approximately 8 mmol/l clamp experiments), but had no effect at basal plasma glucose concentrations. A small increase in cholecystokinin also was observed. Intravenous infusions of synthetic sulphated cholecystokinin-8 leading to plasma concentrations in the upper postprandial range (8–12 pmol/l) did not augment the immunoreactive-insulin or immunoreactive-C-peptide levels during hyperglycaemic clamp experiments, in the absence or presence of elevated plasma phenylalanine concentrations. It is concluded that the augmentation of the glucose-induced insulin release by intraduodenal administration of phenylalanine cannot be related to cholecystokinin release, but rather is explained by the combined effects of elevated glucose and phenylalanine concentrations. In man, cholecystokinin does not augment insulin secretion caused by moderate hyperglycaemia, elevations of phenylalanine concentrations, or combinations thereof.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00277407

    Articles: DFG German National Licenses
  9. 9
    Nauck, M. ; Stöckmann, F. ; Ebert, R. ; Creutzfeldt, W.
    Springer
    Published 1986
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Insulin secretion ; Type 2 (non-insulin-dependent) diabetes ; incretin effect ; gastrointestinal hormones ; gastric inhibitory polypeptide
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Integrated incremental immunoreactive insulin and connecting peptide responses to an oral glucose load of 50 g and an “isoglycaemic” intravenous glucose infusion, respectively, were measured in 14 Type 2 (non-insulin-dependent) diabetic patients and 8 age- and weight-matched metabolically healthy control subjects. Differences between responses to oral and intravenous glucose administration are attributed to factors other than glucose itself (incretin effect). Despite higher glucose increases, immunoreactive insulin and connecting peptide responses after oral glucose were delayed in diabetic patients. Integrated responses were not significantly different between both groups. However, during “isoglycaemic” intravenous infusion, insulin and connecting peptide responses were greater in diabetic patients than in control subjects as a consequence of the higher glycaemic stimulus. The contribution of incretin factors to total insulin responses was 72.8 ± 6.9% (100% = response to oral load) in control subjects and 36.0 ± 8.8% in diabetic patients (p ≦ 0.05). The contribution to connecting peptide responses was 58.4 ± 7.6% in control subjects and 7.6 ± 14.5% (p ≦ 5 0.05) in diabetic patients. Ratios of integrated insulin to connecting peptide responses suggest a reduced (hepatic) insulin extraction in control subjects after oral as compared to intravenous glucose. This was not the case in diabetic patients. Immunoreactive gastric inhibitory polypeptide responses were not different between control subjects and diabetic patients. A reduced or lost incretin effect in the face of normal gastric inhibitory polypeptide response in Type 2 diabetic patients may be explained by decreased sensitivity of the B cells towards the insulinotropic effect of gastric inhibitory polypeptide or to hyposecretion or reduced effectiveness of as yet unidentified humoral or nervous gut factors with incretin activity.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF02427280

    Articles: DFG German National Licenses
  10. 10
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Type 2 (non-insulin-dependent) diabetes mellitus ; incretin hormones ; glucagon-like peptide 1 (7-36 amide) ; pancreatic glucagon ; enteroinsular axis
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Glucagon-like peptide 1 (GLP-1) (7-36 amide) is a physiological incretin hormone that is released after nutrient intake from the lower gut and stimulates insulin secretion at elevated plasma glucose concentrations. Previous work has shown that even in Type 2 (non-insulin-dependent) diabetic patients GLP-1 (7-36 amide) retains much of its insulinotropic action. However, it is not known whether the magnitude of this response is sufficient to normalize plasma glucose in Type 2 diabetic patients with poor metabolic control. Therefore, in 10 Type 2 diabetic patients with unsatisfactory metabolic control (HbAlc 11.6±1.7%) on diet and sulphonylurea therapy (in some patients supplemented by metformin or acarbose), 1.2 pmol ×kg−1×min−1 GLP-1 (7-36 amide) or placebo was infused intravenously in the fasting state (plasma glucose 13.1±0.6 mmol/l). In all patients, insulin (by 17.4±4.7 nmol ×1−1×min; p=0.0157) and C-peptide (by 228.0±39.1 nmol×1−1×min; p=0.0019) increased significantly over basal levels, glucagon was reduced (by -1418±308 pmol ×1−1×min) and plasma glucose reached normal fasting concentrations (4.9±0.3 mmol/l) within 4 h of GLP-1 (7-36 amide) administration, but not with placebo. When normal fasting plasma glucose concentrations were reached insulin returned towards basal levels and plasma glucose concentrations remained stable despite the ongoing infusion of GLP-1 (7-36 amide). Therefore, exogenous GLP-1 (7-36 amide) is an effective means of normalizing fasting plasma glucose concentrations in poorly-controlled Type 2 diabetic patients. The glucose-dependence of insulinotropic actions of GLP-1 (7-36 amide) appears to be retained in such patients.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00401145

    Articles: DFG German National Licenses
  11. 11
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Pancreas transplantation ; Insulin secretion ; C-peptide ; Systemic venous drainage ; Insulin metabolic clearance
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Plasma glucose, immunoreactive insulin and C-peptide concentrations were compared in nine pancreas-kidney-transplanted patients (systemic venous drainage) and in ten non-diabetic kidney-transplanted patients with similar kidney function. In the basal state, C-peptide (insulin secretion) was similar, but immunoreactive insulin was higher and glucose concentrations were slightly, but significantly lower in pancreas-transplanted patients. After 50 g oral glucose, the plasma glucose and IR-insulin profiles were similar in both groups. The circumvention of first-pass hepatic insulin extraction (decreased endogenous insulin clearance) was compensated for by a significant reduction in insulin secretion (C-peptide; p=0.036). In conclusion, hyperinsulinaemia in pancreas-transplanted patients with systemic venous drainage is significant only in the basal state. Insulin delivered into the portal and peripheral circulation, when leading to similar insulin profiles, maintains comparable degrees of glucose tolerance.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00587626

    Articles: DFG German National Licenses
  12. 12
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Keywords Pancreas transplantation ; insulin secretion ; pancreatic hormones ; oral glucose tolerance ; glucagon stimulation
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary After successful pancreas transplantation, insulin-dependent diabetic patients are characterized by a normal or at worst impaired oral glucose tolerance (World Health Organisation criteria). It is not known which pathophysiological mechanisms cause the difference between normal and impaired oral glucose tolerance. Therefore, we studied 41 patients after successful combined pancreas-kidney transplantation using stimulation in the fasting state with oral glucose (75 g), intravenous glucose (0.33 g/kg) and glucagon bolus injection (1 mg i. v.). Glucose (glucose oxidase), insulin and C-peptide (immunoassay) were measured. Repeated-measures analysis of variance and multiple regression analysis were used to analyse the results which showed: 28 patients had a normal, and 13 patients had an impaired oral glucose tolerance. Impaired oral glucose tolerance was associated with a greatly reduced early phase insulin secretory response (insulin p 〈 0.0001; C-peptide p = 0.037). Age (p = 0.65), body mass index (p = 0.94), immunosuppressive therapy (cyclosporin A p = 0.84; predniso(lo)ne p = 0.91; azathioprine p = 0.60) and additional clinical parameters were not different. Reduced insulin secretory responses in patients with impaired oral glucose tolerance were also found with intravenous glucose or glucagon stimulations. Exocrine secretion (α-amylase in 24-h urine collections) also demonstrated reduced pancreatic function in these patients (–46 %; p = 0.04). Multiple regression analysis showed a significant correlation of 120-min glucose with ischaemia time (p = 0.003) and the number of HLA-DR mismatches (p = 0.026), but not with HLA-AB-mismatches (p = 0.084). In conclusion, the pathophysiological basis of impaired oral glucose tolerance after pancreas transplantation is a reduced insulin secretory capacity. Transplant damage is most likely caused by perioperative influences (ischaemia) and by the extent of rejection damage related, for example, to DR-mismatches. [Diabetologia (1996) 39: 462–468]
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00400678

    Articles: DFG German National Licenses
  13. 13
    Ritzel, R. ; Ørskov, C. ; Holst, J. J. ; Nauck, M. A.
    Springer
    Published 1995
    Staff View
    ISSN:
    1432-0428
    Keywords:
    GLP-1 [7–36 amide] ; incretin ; insulin ; glucagon ; pharmacokinetic
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Intravenous infusions of glucagon-like peptide 1 (GLP-1) [7–36 amide] are glucose-dependently insulinotropic and glucagonostatic and normalize plasma glucose concentrations in non-insulin-dependent diabetic patients. It was the aim of this study to investigate whether subcutaneous GLP-1 [7–36 amide] also has an influence on insulin and glucagon secretion, and which doses are required for significant effects. Therefore, eight healthy volunteers (24±2 years, body mass index [BMI] 21.9±2.3 kg/ m2) were studied in the fasting state on five occasions in randomized order. Placebo (0.9% NaCl with 1% human serum albumin) or GLP-1 [7–36 amide] in doses of 0.15, 0.5, 1.5 or 4.5 nmol/kg body weight (volume 1 ml or, at the highest dose, 2 ml) was administered subcutaneously. An intravenous glucose bolus (0.33 g/kg body weight) was injected 30 min later. Blood was drawn for the measurement of glucose, insulin, C-peptide, GLP-1 [7–36 amide], and glucagon using specific radioimmunoassays. There were dose-related increments in GLP-1 [7–36 amide] concentrations (p〈0.0001). However, basal values were reached again after 90–120 min. Before glucose administration, insulin (p〈0.0001) and C-peptide (p〈0.0004) increased, whereas glucagon (p = 0.0018) and glucose (p〈0.0001) decreased in a dose-dependent manner. After glucose stimulation, integrated increments in insulin (p=0.0007) and C-peptide (p=0.02) were augmented and kG-values increased (p〈0.0001) in a dose-related fashion. The extent of reactive hypoglycaemia was related to the GLP-1 [7–36 amide] dose. With the highest GLP-1 [7–36 amide] dose, at the time of peak plasma concentrations, most volunteers felt unwell, and nausea and vomiting were observed in four subjects. In conclusion, subcutaneous GLP-1 [7–36 amide] is also able to stimulate insulin and inhibit glucagon secretion, thereby altering glucose assimilation. However, with unmodified GLP-1 [7–36 amide], the duration of action is short, and with high doses side effects are common.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00401846

    Articles: DFG German National Licenses
  14. 14
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Keywords GLP-1 [7 ; 36 amide] ; incretin ; insulin ; glucagon ; pharmacokinetics.
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Intravenous glucagon-like peptide (GLP)-1 [7–36 amide] can normalize plasma glucose in non-insulin-dependent diabetic (NIDDM) patients. Since this is no form for routine therapeutic administration, effects of subcutaneous GLP-1 at a high dose (1.5 nmol/kg body weight) were examined. Three groups of 8, 9 and 7 patients (61 ± 7, 61 ± 9, 50 ± 11 years; BMI 29.5 ± 2.5, 26.1 ± 2.3, 28.0 ± 4.2 kg/m2; HbA1 c 11.3 ± 1.5, 9.9 ± 1.0, 10.6 ± 0.7 %) were examined: after a single subcutaneous injection of 1.5 nmol/kg GLP [7–36 amide]; after repeated subcutaneous injections (0 and 120 min) in fasting patients; after a single, subcutaneous injection 30 min before a liquid test meal (amino acids 8 %, and sucrose 50 g in 400 ml), all compared with a placebo. Glucose (glucose oxidase), insulin, C-peptide, GLP-1 and glucagon (specific immunoassays) were measured. Gastric emptying was assessed with the indicator-dilution method and phenol red. Repeated measures ANOVA was used for statistical analysis. GLP-1 injection led to a short-lived increment in GLP-1 concentrations (peak at 30–60 min, then return to basal levels after 90–120 min). Each GLP-1 injection stimulated insulin (insulin, C-peptide, p 〈 0.0001, respectively) and inhibited glucagon secretion (p 〈 0.0001). In fasting patients the repeated administration of GLP-1 normalized plasma glucose (5.8 ± 0.4 mmol/l after 240 min vs 8.2 ± 0.7 mmol/l after a single dose, p = 0.0065). With the meal, subcutaneous GLP-1 led to a complete cessation of gastric emptying for 30–45 min (p 〈 0.0001 statistically different from placebo) followed by emptying at a normal rate. As a consequence, integrated incremental glucose responses were reduced by 40 % (p = 0.051). In conclusion, subcutaneous GLP-1 [7–36 amide] has similar effects in NIDDM patients as an intravenous infusion. Preparations with retarded release of GLP-1 would appear more suitable for therapeutic purposes because elevation of GLP-1 concentrations for 4 rather than 2 h (repeated doses) normalized fasting plasma glucose better. In the short term, there appears to be no tachyphylaxis, since insulin stimulation and glucagon suppression were similar upon repeated administrations of GLP-1 [7–36 amide]. It may be easier to influence fasting hyperglycaemia by GLP-1 than to reduce meal-related increments in glycaemia. [Diabetologia (1996) 39: 1546–1553]
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/s001250050613

    Articles: DFG German National Licenses
  15. 15
    Ritzel, R. ; Ørskov, C. ; Holst, J. J. ; Nauck, M. A.
    Springer
    Published 1995
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Key words GLP-1 [7 ; 36 amide] ; incretin ; insulin ; glucagon ; pharmacokinetics
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Intravenous infusions of glucagon-like peptide 1 (GLP-1) [7–36 amide] are glucose-dependently insulinotropic and glucagonostatic and normalize plasma glucose concentrations in non-insulin-dependent diabetic patients. It was the aim of this study to investigate whether subcutaneous GLP-1 [7–36 amide] also has an influence on insulin and glucagon secretion, and which doses are required for significant effects. Therefore, eight healthy volunteers (24 ± 2 years, body mass index [BMI] 21.9 ± 2.3 kg/m2) were studied in the fasting state on five occasions in randomized order. Placebo (0.9 % NaCl with 1 % human serum albumin) or GLP-1 [7–36 amide] in doses of 0.15, 0.5, 1.5 or 4.5 nmol/kg body weight (volume 1 ml or, at the highest dose, 2 ml) was administered subcutaneously. An intravenous glucose bolus (0.33 g/kg body weight) was injected 30 min later. Blood was drawn for the measurement of glucose, insulin, C-peptide, GLP-1 [7–36 amide], and glucagon using specific radioimmunoassays. There were dose-related increments in GLP-1 [7–36 amide] concentrations (p 〈 0.0001). However, basal values were reached again after 90–120 min. Before glucose administration, insulin (p 〈 0.0001) and C-peptide (p 〈 0.0004) increased, whereas glucagon (p = 0.0018) and glucose (p 〈 0.0001) decreased in a dose-dependent manner. After glucose stimulation, integrated increments in insulin (p = 0.0007) and C-peptide (p = 0.02) were augmented and kG-values increased (p 〈 0.0001) in a dose-related fashion. The extent of reactive hypoglycaemia was related to the GLP-1 [7–36 amide] dose. With the highest GLP-1 [7–36 amide] dose, at the time of peak plasma concentrations, most volunteers felt unwell, and nausea and vomiting were observed in four subjects. In conclusion, subcutaneous GLP-1 [7–36 amide] is also able to stimulate insulin and inhibit glucagon secretion, thereby altering glucose assimilation. However, with unmodified GLP-1 [7–36 amide], the duration of action is short, and with high doses side effects are common. [Diabetologia (1995) 38: 720–725]
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00401846

    Articles: DFG German National Licenses
  16. 16
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Pancreas transplantation ; insulin secretion ; pancreatic hormones ; oral glucose tolerance ; glucagon stimulation
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary After successful pancreas transplantation, insulin-dependent diabetic patients are characterized by a normal or at worst impaired oral glucose tolerance (World Health Organisation criteria). It is not known which pathophysiological mechanisms cause the difference between normal and impaired oral glucose tolerance. Therefore, we studied 41 patients after successful combined pancreas-kidney transplantation using stimulation in the fasting state with oral glucose (75 g), intravenous glucose (0.33 g/kg) and glucagon bolus injection (1 mg i.v.). Glucose (glucose oxidase), insulin and C-peptide (immunoassay) were measured. Repeated-measures analysis of variance and multiple regression analysis were used to analyse the results which showed: 28 patients had a normal, and 13 patients had an impaired oral glucose tolerance. Impaired oral glucose tolerance was associated with a greatly reduced early phase insulin secretory response (insulin p〈0.0001; C-peptide p=0.037). Age (p=0.65), body mass index (p=0.94), immunosuppressive therapy (cyclosporin A p=0.84; predniso(lo)ne p=0.91; azathioprine p=0.60) and additional clinical parameters were not different. Reduced insulin secretory responses in patients with impaired oral glucose tolerance were also found with intravenous glucose or glucagon stimulations. Exocrine secretion (α-amylase in 24-h urine collections) also demonstrated reduced pancreatic function in these patients (−46%; p=0.04). Multiple regression analysis showed a significant correlation of 120-min glucose with ischaemia time (p=0.003) and the number of HLA-DR mismatches (p=0.026), but not with HLA-AB-mismatches (p=0.084). In conclusion, the pathophysiological basis of impaired oral glucose tolerance after pancreas transplantation is a reduced insulin secretory capacity. Transplant damage is most likely caused by perioperative influences (ischaemia) and by the extent of rejection damage related, for example, to DR-mismatches.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00400678

    Articles: DFG German National Licenses
  17. 17
    Holst, J. J. ; Gromada, J. ; Nauck, M. A.
    Springer
    Published 1997
    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/s001250050779

    Articles: DFG German National Licenses
  18. 18
    Staff View
    ISSN:
    1432-0428
    Keywords:
    Keywords Insulin secretion, protein kinase, insulin secreting cells, human CaMK II, cloning of new subtypes.
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Aims/hypothesis. The Ca2+/calmodulin-dependent protein kinase II (CaMK II) is highly expressed in pancreatic islets and associated with insulin secretion vesicles. The suppression of CaMK II disturbs insulin secretion and insulin gene expression. There are four isoforms of CaMK II, α to δ, that are expressed from different genes in mammals. Our aim was to identify the isoforms of CaMK II expressed in human beta cells by molecular cloning from a human insulinoma cDNA library and to assess its distribution in humans.¶Methods. The previously unknown complete coding sequences of human CaMK II β and the kinase domain of CaMK II δ were cloned from a human insulinoma cDNA library. Quantitative determination of CaMK II isoform mRNA was carried out in several tissues and beta cells purified by fluorescence activated cell sorting and compared to the housekeeping enzyme pyruvate dehydrogenase.¶Results. We found CaMK IIβ occurred in three splice variants and was highly expressed in endocrine tissues such as adrenals, pituitary and beta cells. Liver showed moderate expression but adipose tissue or lymphocytes had very low levels of CaMK II β-mRNA. In human beta cells CaMK II β and δ were expressed equally with pyruvate dehydrogenase whereas tenfold lower expression of CaMK II γ and no expression of CaMK IIα were found.¶Conclusion/interpretation. Although CaMK II δ is ubiquitously expressed, CaMK II β shows preferential expression in neuroendocrine tissues. In comparison with the expression of a key regulatory enzyme in glucose oxidation, pyruvate dehydrogenase, two of the four CaM kinases investigated are expressed at equally high levels, which supports an important role in beta-cell physiology. These results provide the basis for exploring the pathophysiological relevance of CaMK IIβ in human diabetes. [Diabetologia (2000) 43: 465–473]
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/s001250051330

    Articles: DFG German National Licenses
  19. 19
    Staff View
    ISSN:
    1432-5233
    Keywords:
    Key words Glucagon-like peptide 1 ; Leptin ; Obesity ; C-peptide
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Glucagon-like peptide 1 [7–36 amide] (GLP-1) and the obese gene product (leptin) are thought to be involved in the central regulation of feeding. Both may act from the peripheral circulation to influence brain function. To study potential interactions, GLP-1 ([7–36 amide]: 0.4, 0.8 pmol kg–1 min–1 or placebo on separate occasions) was infused intravenously (from –30 to 240 min) into nine healthy volunteers [age 26±3 years, body mass index: 22.9±1.6 kg/m2, glycated haemoglobin HbA1c: 5.0%± 0.2% (normal: 4.0%–6.2%), creatinine: 1.1±0.1 mg/dl], and (at 0 min) a liquid test meal (50 g sucrose in 400 ml 8% amino acid, total amino acids 80 g/l) was administered via a nasogastric tube. Plasma leptin (radioimmunoassay, RIA), glucose, insulin (microparticle enzyme immunoassay), C-peptide (enzyme-linked immunosorbent assay) and GLP-1 (RIA) were measured, and statistical analysis was done with repeated-measures ANOVA and Student's t-test. Plasma leptin concentrations were 31±6 pmol/l in the basal state. They did not change within 240 min after meal ingestion nor in response to the infusion of exogenous GLP-1 [7–36 amide] (P=0.99 for the interaction of experiment and time) leading to GLP-1 mean plasma levels of 25±2 and 36±3 (basal 6±1) pmol/l. On the other hand, glucose (from basal 4.7±0.1 to 6.0±0.2 mmol/l at 15 min, P〈0.05) and insulin (from basal 28±2 to 325±78 pmol/l at 45 min, P〈0.05) increased clearly after the meal with placebo. In conclusion, (1) plasma leptin levels in normal human subjects show no short-term changes after feeding a liquid mixed meal and (2) do not appear to be directly influenced by physiological and pharmacological elevations in plasma GLP-1 [7–36 amide] concentrations. This does not exclude interactions at the cerebral (hypothalamic) level or on more long-term temporal scales.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/s005920050079

    Articles: DFG German National Licenses
  20. 20
    Nauck, M. A.
    Springer
    Published 1998
    Staff View
    ISSN:
    1432-5233
    Keywords:
    Key words Incretin ; Gastric inhibitory polypeptide ; Glucagon-like peptide 1 ; Gut hormones ; Type 2 diabetes ; Type 1 diabetes ; Obesity ; New treatment modalities
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract Glucagon-like peptide 1 (GLP-1) is a physiological incretin hormone from the lower gastrointestinal tract, partially explaining the augmented insulin response after oral compared to intravenous glucose administration in normal humans. In addition, GLP-1 also lowers glucagon concentrations, slows gastric emptying, stimulates (pro)insulin biosynthesis, and reduces food intake upon intracerebroventricular administration in animals. Therefore, GLP-1 offers some interesting perspective for the treatment of type 2, and perhaps also for type 1 diabetic patients. The other incretin hormone, gastric inhibitory polypeptide (GIP), has lost almost all its activity in type-2 diabetic patients. In contrast, GLP-1 glucose-dependently stimulates insulin secretion in type-2 diabetic patients and exogenous administration of GLP-1 ([7–37] or [7–36 amide]) in doses elevating plasma concentrations to approximately three to four times physiological postprandial levels fully normalizes fasting hyperglycaemia and reduces postprandial glycaemic increments. Due to rapid proteolytic cleavage, which results in an inactive or even antagonistic fragment, GLP-1 [9–36 amide], and to rapid elimination, the half-life of GLP-1 is too short to maintain therapeutic plasma levels for sufficient periods by subcutaneous injections of the natural peptide hormone. Current research aims to characterize GLP-1 analogues with more suitable pharmacokinetic properties than the original peptide. Given the large amount of GLP-1 present in L cells, it also appears worthwhile to search for more agents that could `mobilize' this endogenous pool of GLP-1.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/s005920050116

    Articles: DFG German National Licenses