Sökning: onr:"swepub:oai:DiVA.org:uu-124752" > Detailed physiologi...
Fältnamn | Indikatorer | Metadata |
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000 | 06005naa a2201093 4500 | |
001 | oai:DiVA.org:uu-124752 | |
003 | SwePub | |
008 | 100505s2010 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1247522 URI |
024 | 7 | a https://doi.org/10.2337/db09-15682 DOI |
040 | a (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Ingelsson, Eriku Uppsala universitet,Geriatrik4 aut0 (Swepub:uu)ering425 |
245 | 1 0 | a Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans |
264 | c 2010-02-25 | |
264 | 1 | b American Diabetes Association,c 2010 |
338 | a print2 rdacarrier | |
520 | a OBJECTIVE Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes. | |
653 | a MEDICINE | |
653 | a MEDICIN | |
700 | 1 | a Langenberg, Claudia4 aut |
700 | 1 | a Hivert, Marie-France4 aut |
700 | 1 | a Prokopenko, Inga4 aut |
700 | 1 | a Lyssenko, Valeriya4 aut |
700 | 1 | a Dupuis, Josée4 aut |
700 | 1 | a Mägi, Reedik4 aut |
700 | 1 | a Sharp, Stephen4 aut |
700 | 1 | a Jackson, Anne U.4 aut |
700 | 1 | a Assimes, Themistocles L.4 aut |
700 | 1 | a Shrader, Peter4 aut |
700 | 1 | a Knowles, Joshua W.4 aut |
700 | 1 | a Zethelius, Björnu Uppsala universitet,Geriatrik4 aut0 (Swepub:uu)bjorzeth |
700 | 1 | a Abbasi, Fahim A.4 aut |
700 | 1 | a Bergman, Richard N.4 aut |
700 | 1 | a Bergmann, Antje4 aut |
700 | 1 | a Berne, Christianu Uppsala universitet,Institutionen för medicinska vetenskaper,Endokrinologi och diabetes4 aut0 (Swepub:uu)chber255 |
700 | 1 | a Boehnke, Michael4 aut |
700 | 1 | a Bonnycastle, Lori L.4 aut |
700 | 1 | a Bornstein, Stefan R.4 aut |
700 | 1 | a Buchanan, Thomas A.4 aut |
700 | 1 | a Bumpstead, Suzannah J.4 aut |
700 | 1 | a Böttcher, Yvonne4 aut |
700 | 1 | a Chines, Peter4 aut |
700 | 1 | a Collins, Francis S.4 aut |
700 | 1 | a Cooper, Cyrus C.4 aut |
700 | 1 | a Dennison, Elaine M.4 aut |
700 | 1 | a Erdos, Michael R.4 aut |
700 | 1 | a Ferrannini, Ele4 aut |
700 | 1 | a Fox, Caroline S.4 aut |
700 | 1 | a Graessler, Jürgen4 aut |
700 | 1 | a Hao, Ke4 aut |
700 | 1 | a Isomaa, Bo4 aut |
700 | 1 | a Jameson, Karen A.4 aut |
700 | 1 | a Kovacs, Peter4 aut |
700 | 1 | a Kuusisto, Johanna4 aut |
700 | 1 | a Laakso, Markku4 aut |
700 | 1 | a Ladenvall, Claes4 aut |
700 | 1 | a Mohlke, Karen L.4 aut |
700 | 1 | a Morken, Mario A.4 aut |
700 | 1 | a Narisu, Narisu4 aut |
700 | 1 | a Nathan, David M.4 aut |
700 | 1 | a Pascoe, Laura4 aut |
700 | 1 | a Payne, Felicity4 aut |
700 | 1 | a Petrie, John R.4 aut |
700 | 1 | a Sayer, Avan A.4 aut |
700 | 1 | a Schwarz, Peter E. H.4 aut |
700 | 1 | a Scott, Laura J.4 aut |
700 | 1 | a Stringham, Heather M.4 aut |
700 | 1 | a Stumvoll, Michael4 aut |
700 | 1 | a Swift, Amy J.4 aut |
700 | 1 | a Syvänen, Ann-Christineu Uppsala universitet,Molekylär medicin4 aut0 (Swepub:uu)anncsyva |
700 | 1 | a Tuomi, Tiinamaija4 aut |
700 | 1 | a Tuomilehto, Jaakko4 aut |
700 | 1 | a Tönjes, Anke4 aut |
700 | 1 | a Valle, Timo T.4 aut |
700 | 1 | a Williams, Gordon H.4 aut |
700 | 1 | a Lind, Larsu Uppsala universitet,Institutionen för medicinska vetenskaper4 aut0 (Swepub:uu)laeli995 |
700 | 1 | a Barroso, Inês4 aut |
700 | 1 | a Quertermous, Thomas4 aut |
700 | 1 | a Walker, Mark4 aut |
700 | 1 | a Wareham, Nicholas J.4 aut |
700 | 1 | a Meigs, James B.4 aut |
700 | 1 | a McCarthy, Mark I.4 aut |
700 | 1 | a Groop, Leif4 aut |
700 | 1 | a Watanabe, Richard M.4 aut |
700 | 1 | a Florez, Jose C.4 aut |
710 | 2 | a Uppsala universitetb Geriatrik4 org |
773 | 0 | t Diabetesd : American Diabetes Associationg 59:5, s. 1266-1275q 59:5<1266-1275x 0012-1797x 1939-327X |
856 | 4 | u https://diabetes.diabetesjournals.org/content/diabetes/59/5/1266.full.pdf |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-124752 |
856 | 4 8 | u https://doi.org/10.2337/db09-1568 |
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