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- Boesgaard, T. W., et al.
(författare)
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Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients--EUGENE2 study
- 2009
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Ingår i: PLoS One. - 1932-6203. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKROUND: A meta-analysis combining results from three genome-wide association studies and followed by large-scale replication identified six novel type 2 diabetes loci. Subsequent studies of the effect of these variants on estimates of the beta-cell function and insulin sensitivity have been inconclusive. We examined these variants located in or near the JAZF1 (rs864745), THADA (rs7578597), TSPAN8 (rs7961581), ADAMTS9 (rs4607103), NOTCH2 (rs10923931) and the CDC123/CAMK1D (rs12779790) genes for associations with measures of pancreatic beta-cell function and insulin sensitivity. METHODOLOGY/RESULTS: Oral and intravenous glucose stimulated insulin release (n = 849) and insulin sensitivity (n = 596) estimated from a hyperinsulinemic euglycemic clamp were measured in non-diabetic offspring of type 2 diabetic patients from five European populations. Assuming an additive genetic model the diabetes-associated major C-allele of rs4607103 near ADAMTS9 associated with reduced insulin-stimulated glucose uptake (p = 0.002) during a hyperinsulinemic euglycemic clamp. However, following intravenous and oral administration of glucose serum insulin release was increased in individuals with the C-allele (p = 0.003 and p = 0.01, respectively). A meta-analyse combining clamp and IVGTT data from a total of 905 non-diabetic individuals showed that the C-risk allele associated with decreased insulin sensitivity (p = 0.003) and increased insulin release (p = 0.002). The major T-allele of the intronic JAZF1 rs864745 conferring increased diabetes risk was associated with increased 2(nd) phase serum insulin release during an IVGTT (p = 0.03), and an increased fasting serum insulin level (p = 0.001). The remaining variants did not show any associations with insulin response, insulin sensitivity or any other measured quantitative traits. CONCLUSION: The present studies suggest that the diabetogenic impact of the C-allele of rs4607103 near ADAMTS9 may in part be mediated through decreased insulin sensitivity of peripheral tissues.
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| 2. |
- Andersson, U.B., et al.
(författare)
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Characterization of the Paleoproterozoic Mantle beneath the Fennoscandian Shield : Geochemistry and Isotope Geology (Nd, Sr) of ~ 1.8 Ga Mafic Plutonic Rocks from the Transscandinavian Igneous Belt in Southeast Sweden
- 2007
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Ingår i: International Geology Review. - : Informa UK Limited. - 0020-6814 .- 1938-2839. ; 49:7, s. 587-625
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Forskningsöversikt (refereegranskat)abstract
- Geochemistry and Sr-Nd isotope geochemistry of ca. 1.8 Ga, mafic intrusions of the Transscandinavian Igneous Belt (TIB-1) in the Fennoscandian shield were studied in southeastern Sweden. These rocks show LILE-LREE-enriched, HFSE-depleted, calc-alkaline, continental arc signatures in the north, grading to slightly less enriched, oceanic affinities southward.εNd(1.80) values range from +2.0 to +0.7 and 87Sr/86Sr(1.80) from 0.7022 to 0.7029 (with one outlier at 0 and 0.7033), without correlation to fractionation (e.g., Mg#) or crustal contamination, indicating sources that are mildly depleted. The most depleted ratios occur in the south, trending with the geochemistry toward more enriched compositions northward. The sources represent depleted mantle wedge material that was subjected to enrichment not long before (TDM ca. 2.0 Ga), i.e., during the preceding arc subduction (2.1-1.82 Ga), and/or during the TIB-1 magmatism itself, by hydrous fluids with a sediment and/or melt input increasing northward. The TIB-1 magmatism occurred above a south(west)ward-retreating subduction zone along the continental margin of the juvenile Svecofennian continent at 1.81-1.76 Ga.
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| 5. |
- Rutanen, H, et al.
(författare)
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1.8 Ga magmatism in southern Finland : strongly enriched mantle and juvenile crustal sources in a post-collisional setting
- 2011
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Ingår i: International Geology Review. - : Informa UK Limited. - 0020-6814 .- 1938-2839. ; 53:14, s. 1622-1683
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Tidskriftsartikel (refereegranskat)abstract
- Whole-rock and isotope geochemistry of six similar to 1.8 Ga post-kinematic intrusions, emplaced along the similar to 1.9 Ga Southern Svecofennian Arc Complex (SSAC) and in the SW part of the Karelian Domain in Finland, was studied. The intrusive age [U-Pb secondary ion mass spectrometer (SIMS)] of one of these, the Petravaara Pluton, was determined as 1811 +/- 6 Ma. Basic-intermediate rocks are alkali-rich (K(2)O + Na(2)O > 4 wt.%) and typically shoshonitic, strongly enriched in large ion lithophile elements and light rare earth elements, but relatively depleted in high field strength elements and heavy rare earth elements. The enrichment is much higher than can be accounted for by crustal contamination and requires previously melt-depleted mantle sources, subjected to variable metasomatism by carbonate-rich fluids and sediment-derived melts. These sources are inferred to consist of phlogopite +/- amphibole-bearing peridotites from depths below the spinel-garnet transition, as shown by the high Ce/Yb ratios. (87)Sr/(86)Sr(1.8 Ga) ratios in the range 0.7027-0.7031 and 'mildly depleted' epsilon(Nd)(1.8 Ga) values (+0.1 to +1.4), with T(DM) values <2.1 Ga, suggest that mantle enrichment was associated with the previous Svecofennian subduction-accretion process, when enriched sub-Svecofennian mantle sections developed, dominantly characterized by (147)Sm/(144)Nd ratios of 0.14-0.17. The associated granitoids are diversified. One group is marginally peraluminous, transitional between I (volcanic-arc) and S (syn-collisional) types, and was derived from mixed igneous and sedimentary, but juvenile Svecofennian source rocks, as supported by near-chondritic epsilon(Nd)(1.8 Ga) and somewhat elevated (87)Sr/(86)Sr(1.8 Ga). The other group is transitional between I and A (within-plate) types in character and had dominantly igneous protoliths. The whole-rock geochemistry and isotopes suggest that the compositional variation between similar to 50 and 70 wt.% SiO(2) may be explained by hybridization between strongly enriched mantle-derived magmas and anatectic granitic magmas from the juvenile Svecofennian crust. One intrusion in the east contains a significant portion of Archaean, mostly igneous protolithic material (epsilon(Nd)(1.8 Ga) = -2.8 and epsilon(Hf)(t) for zircons between +2.8 and -11.9, with an average of -4.9). The similar to 1.8 Ga post-kinematic intrusions were emplaced within the SSAC subsequent to the continental collision with the Volgo-Sarmatia craton from the SE, during a shift from contraction to extension, that is, in a post-collisional setting.
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