Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans

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Fältnamn	Indikatorer	Metadata
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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Av författaren/redakt...: Ingelsson, Erik; Langenberg, Clau ...; Hivert, Marie-Fr ...; Prokopenko, Inga; Lyssenko, Valeri ...; Dupuis, Josée; visa fler...; Mägi, Reedik; Sharp, Stephen; Jackson, Anne U.; Assimes, Themist ...; Shrader, Peter; Knowles, Joshua ...; Zethelius, Björn; Abbasi, Fahim A.; Bergman, Richard ...; Bergmann, Antje; Berne, Christian; Boehnke, Michael; Bonnycastle, Lor ...; Bornstein, Stefa ...; Buchanan, Thomas ...; Bumpstead, Suzan ...; Böttcher, Yvonne; Chines, Peter; Collins, Francis ...; Cooper, Cyrus C.; Dennison, Elaine ...; Erdos, Michael R ...; Ferrannini, Ele; Fox, Caroline S.; Graessler, Jürge ...; Hao, Ke; Isomaa, Bo; Jameson, Karen A ...; Kovacs, Peter; Kuusisto, Johann ...; Laakso, Markku; Ladenvall, Claes; Mohlke, Karen L.; Morken, Mario A.; Narisu, Narisu; Nathan, David M.; Pascoe, Laura; Payne, Felicity; Petrie, John R.; Sayer, Avan A.; Schwarz, Peter E ...; Scott, Laura J.; Stringham, Heath ...; Stumvoll, Michae ...; Swift, Amy J.; Syvänen, Ann-Chr ...; Tuomi, Tiinamaij ...; Tuomilehto, Jaak ...; Tönjes, Anke; Valle, Timo T.; Williams, Gordon ...; Lind, Lars; Barroso, Inês; Quertermous, Tho ...; Walker, Mark; Wareham, Nichola ...; Meigs, James B.; McCarthy, Mark I ...; Groop, Leif; Watanabe, Richar ...; Florez, Jose C.; visa färre...

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