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- Ingelsson, Erik, et al.
(författare)
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Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans
- 2010
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Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 59:5, s. 1266-1275
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Konferensbidrag (refereegranskat)abstract
- 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. Diabetes 59:1266-1275, 2010
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| 3. |
- Igochine, Valentin, et al.
(författare)
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Identification of the beta limit in ASDEX Upgrade
- 2013
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Ingår i: 40th EPS Conference on Plasma Physics, EPS 2013, Espoo, Finland, 1-5 July 2013. - 9781632663108 ; 2, s. 1414-1417
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Konferensbidrag (refereegranskat)abstract
- Tokamak plasma is a subject of various resistive and ideal MHD instabilities which restrict the operation space of the device. For largest fusion outcome, it is preferable to operate the tokamak close to the stability limit with maximal possible pressure characterized by the value of normalized beta, , and thus maximal fusion power . In ASDEX Upgrade, the limit for maximal achievable is typically set by the resistive instabilities (tearing modes). If these instabilities are overcome or prevented, higher values of the normalized beta can be reached limited by the onset of the ideal kink instability. The actual limit depends on several factors, including the stabilizing influence of the conducting components facing the plasma surface. At present, the wall elements are far from the plasma and the stability boundary is expected to be close to the “no wall” limit (no stabilizing wall effect). Investigation of maximum achievable βN values for the different operation scenario in ASDEX Upgrade is presented in this work. Two indicators are used to detect the stability boundary:Increase of the resonant field amplification (RFA)Onset of the ideal kink modeRecently installed internal active coils are used to probe stability of the plasma by the RFA technique. A wide range of different MHD diagnostics are used to identify the behaviour and structure of MHD modes in different discharges with high . Experimentally obtained results are compared with the results of the numerical modelling with linear MHD codes CASTOR-FLOW and MARS-K. Such comparison allows to validate the plasma model used in the codes and therefore to make numerical projection for further experimental studies.
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