| 1. |
- Williamson, Alice, et al.
(author)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Journal article (peer-reviewed)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 2. |
- Broadaway, K Alaine, et al.
(author)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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In: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Journal article (peer-reviewed)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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| 3. |
- Ning, F., et al.
(author)
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Does abnormal insulin action or insulin secretion explain the increase in prevalence of impaired glucose metabolism with age in populations of different ethnicities?
- 2010
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In: DIABETES-METABOLISM RESEARCH AND REVIEWS. - 1520-7552. ; 26:4, s. 245-253
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Journal article (peer-reviewed)abstract
- Background Age is associated with both impaired glucose and insulin metabolism. To what extent the age-related changes in insulin resistance (IR) and β-cell function contribute to the increase in prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) is less known, and this is investigated in this study. Methods This study included 6610 men and 7664 women of different ethnic groups aged 30-69 years. IR and β-cell function were examined by the homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-B). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression analysis adjusting for body mass index and study. Results In Chinese men, the ORs (95% CIs) for IFG were 2.69 (1.70, 4.26), 2.51 (1.49, 4.21) and 2.89 (1.68, 4.97), respectively, in age groups of 40–49, 50–59 and 60–69 years compared with 30–39 years (p < 0.001 for trend); the corresponding figures for IGT were 1.73 (1.25, 2.38), 2.54 (1.78, 3.63) and 3.57 (2.46, 5.19) (p < 0.001 for trend). Similar trends for IGT were observed also in Chinese women and other ethnic groups, but not for IFG in Mauritius Indian and Creole men. Adjustment for HOMA-IR and HOMA-B reduced the ORs in all age groups of all ethnicities for both IFG and IGT, but the risk gradient between age groups remained particularly for the IGT. Conclusions The age-related increase in glucose intolerance may not be fully explained by the defect in HOMA-IR and HOMA-B. As HOMA-IR and HOMA-B are only surrogate measures of insulin sensitivity and insulin secretion, the results need to be further investigated
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| 4. |
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| 5. |
- Wahlstrom, I., et al.
(author)
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Projected climate change impact on a coastal sea-As significant as all current pressures combined
- 2022
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:17, s. 5310-5319
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Journal article (peer-reviewed)abstract
- Climate change influences the ocean's physical and biogeochemical conditions, causing additional pressures on marine environments and ecosystems, now and in the future. Such changes occur in environments that already today suffer under pressures from, for example, eutrophication, pollution, shipping, and more. We demonstrate how to implement climate change into regional marine spatial planning by introducing data of future temperature, salinity, and sea ice cover from regional ocean climate model projections to an existing cumulative impact model. This makes it possible to assess climate change impact in relation to pre-existing cumulative impact from current human activities. Results indicate that end-of-century projected climate change alone is a threat of the same magnitude as the combination of all current pressures to the marine environment. These findings give marine planners and policymakers forewarning on how future climate change may impact marine ecosystems, across space, emission scenarios, and in relation to other pressures.
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| 6. |
- Hammar, Mats, et al.
(author)
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Tibolone and low-dose continuous combined hormone treatment : Vaginal bleeding pattern, efficacy and tolerability
- 2007
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In: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 114:12, s. 1522-1529
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Journal article (peer-reviewed)abstract
- Objectives: The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E2/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy. Design: A randomised, double-blind, double-dummy, group comparative intervention trial. Setting: Multicentre study executed in 32 centres in 7 European countries. Sample: Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45-65 years. Methods: Participants were randomised to receive 2.5 mg tibolone or 1 mg 17ß estradiol plus 0.5 mg norethisterone acetate (E 2/NETA) daily for 48 weeks. Main outcome measures: Prevalence of vaginal bleeding, hot flushes and adverse events. Results: The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%, P < 0.001) when compared with the E 2/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7-9 months of treatment (11 versus 19%, P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E2/NETA (3.2 versus 9.8%, P < 0.001). Conclusion: Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy. © 2007 The Authors.
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| 7. |
- Streubel, K., et al.
(author)
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Novel technologies for 1.55-mu m vertical cavity lasers
- 2000
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In: Optical Engineering. - : SPIE-Intl Soc Optical Eng. - 0091-3286 .- 1560-2303. ; 39:2, s. 488-497
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Journal article (peer-reviewed)abstract
- We report on three novel vertical-cavity laser (VCL) structures for 1.55-mu m operation. Two of the structures utilize an n-type GalnAsP/InP Bragg mirror combined with an Al(Ga)As/GaAs mirror using either wafer fusion or metamorphic epitaxial growth. The third employs two wafer-fused AlGaAs/GaAs mirrors, in which lateral current confinement is obtained by localized fusion of the p mirror. Ali three VCLs use strained GalnAsP quantum welts as active material and achieve continuous-wave (cw) operation at room temperature or above. The single fused VCL operates up to 17 and 101 degrees C in continuous-wave and pulsed mode, respectively. The monolithic VCL-structure with a metamorphic GaAs/AlAs n-type mirror uses a reverse-biased tunnel junction for current injection. This laser achieves record high output power (1 mW) at room temperature and operates cw up to 45 degrees C. The double fused VCLs with a 10x10-mu m(2) active area operate cw up to 30 degrees C with threshold current as low as 2.5 mA and series resistance of 30 Omega. The emission spectra exhibit a single lasing mode polarized with 30-dB extinction ratio and a spectral linewidth of 150 MHz.
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| 8. |
- Vukusic, J., et al.
(author)
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MOVPE-grown GaInNAsVCSELs at 1.3 mu m with conventional mirror design approach
- 2003
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In: Electronics Letters. - : Institution of Engineering and Technology (IET). - 0013-5194 .- 1350-911X. ; 39:8, s. 662-664
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Journal article (peer-reviewed)abstract
- 1.3 mum oxide confined GaInNAs VCSELs designed using the same design philosophy used for standard 850 nm VCSELs is presented. The VCSELs have doped mirrors, with graded and highly doped interfaces, and are fabricated using production-friendly procedures. Multimode VCSELs (I I mum oxide aperture) with an emission wavelength of 1287 nm have a threshold current of 3 mA and produce I mW of output power at 20degreesC. The maximum operating temperature is 95degreesC. Emission at 1303 nm with I mW of output power and a threshold current of 7 mA has been observed from VCSELs with a larger detuning between the gain peak and the cavity resonance.
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| 9. |
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| 10. |
- Zwiller, V., et al.
(author)
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Studies of self-assembled InP quantum dots in planar microcavities
- 2000
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In: Materials Science and Engineering B: Solid-State Materials for Advanced Technology. - Strasbourg, France. ; 69:Lausanne, Switzerland, s. 314-317
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Journal article (peer-reviewed)abstract
- Self-assembled InP quantum dots have been grown in planar microcavities. The dots were embedded in a Ga0.52In0.48P spacer grown on top of a high reflectance epitaxial Al0.29Ga0.71As/AlAs distributed Bragg reflector (DBR) to obtain a 33λ/4 cavity. The Fabry-Perot microcavity is formed between the AlGaAs/AlAs DBR and a dielectric SiNx/SiO2 DBR deposited on top of the GaInP spacer. The quantum dot emission is centered at 1.62 eV at 7 K. The microcavity resonance is centered at 1.65 eV, with a linewidth of 2 meV. Micro-photoluminescence (PL) studies using different objectives with different numerical apertures enable the collection of transversal modes.
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