| 1. |
- Williamson, Alice, et al.
(författare)
-
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Broadaway, K Alaine, et al.
(författare)
-
Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
-
Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 3. |
- Ning, F., et al.
(författare)
-
Does abnormal insulin action or insulin secretion explain the increase in prevalence of impaired glucose metabolism with age in populations of different ethnicities?
- 2010
-
Ingår i: DIABETES-METABOLISM RESEARCH AND REVIEWS. - 1520-7552. ; 26:4, s. 245-253
-
Tidskriftsartikel (refereegranskat)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
|
|
| 4. |
|
|
| 5. |
- Wahlstrom, I., et al.
(författare)
-
Projected climate change impact on a coastal sea-As significant as all current pressures combined
- 2022
-
Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:17, s. 5310-5319
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 6. |
- Hammar, Mats, et al.
(författare)
-
Tibolone and low-dose continuous combined hormone treatment : Vaginal bleeding pattern, efficacy and tolerability
- 2007
-
Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 114:12, s. 1522-1529
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 7. |
- Streubel, K., et al.
(författare)
-
Novel technologies for 1.55-mu m vertical cavity lasers
- 2000
-
Ingår i: Optical Engineering. - : SPIE-Intl Soc Optical Eng. - 0091-3286 .- 1560-2303. ; 39:2, s. 488-497
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 8. |
- Vukusic, J., et al.
(författare)
-
MOVPE-grown GaInNAsVCSELs at 1.3 mu m with conventional mirror design approach
- 2003
-
Ingår i: Electronics Letters. - : Institution of Engineering and Technology (IET). - 0013-5194 .- 1350-911X. ; 39:8, s. 662-664
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 9. |
|
|
| 10. |
- Zwiller, V., et al.
(författare)
-
Studies of self-assembled InP quantum dots in planar microcavities
- 2000
-
Ingår i: Materials Science and Engineering B: Solid-State Materials for Advanced Technology. - Strasbourg, France. ; 69:Lausanne, Switzerland, s. 314-317
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Almby, Kristina E., et al.
(författare)
-
Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery
- 2019
-
Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 181:2, s. 161-171
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).Design: Experimental hyperinsulinemic–hypoglycemic clamp study.Methods: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.Conclusions/interpretation: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.
|
|
| 16. |
|
|
| 17. |
- Ashenafi, S, et al.
(författare)
-
Daily Nutritional Supplementation with Vitamin D₃ and Phenylbutyrate to Treatment-Naïve HIV Patients Tested in a Randomized Placebo-Controlled Trial
- 2019
-
Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Poor nutritional status is common among human immunodeficiency virus (HIV)-infected patients including vitamin D (vitD3) deficiency. We conducted a double-blinded, randomized, and placebo-controlled trial in Addis Ababa, Ethiopia, to investigate if daily nutritional supplementation with vitD3 (5000 IU) and phenylbutyrate (PBA, 2 × 500 mg) could mediate beneficial effects in treatment-naïve HIV patients. Primary endpoint: the change in plasma HIV-1 comparing week 0 to 16 using modified intention-to-treat (mITT, n = 197) and per-protocol (n = 173) analyses. Secondary endpoints: longitudinal HIV viral load, T cell counts, body mass index (BMI), middle-upper-arm circumference (MUAC), and 25(OH)D3 levels in plasma. Baseline characteristics were detectable viral loads (median 7897 copies/mL), low CD4+ (median 410 cells/µL), and elevated CD8+ (median 930 cells/µL) T cell counts. Most subjects were vitD3 deficient at enrolment, but a gradual and significant improvement of vitD3 status was demonstrated in the vitD3 + PBA group compared with placebo (p < 0.0001) from week 0 to 16 (median 37.5 versus 115.5 nmol/L). No significant changes in HIV viral load, CD4+ or CD8+ T cell counts, BMI or MUAC could be detected. Clinical adverse events were similar in both groups. Daily vitD3 + PBA for 16 weeks was well-tolerated and effectively improved vitD3 status but did not reduce viral load, restore peripheral T cell counts or improve BMI or MUAC in HIV patients with slow progressive disease. Clinicaltrials.gov NCT01702974.
|
|
| 18. |
- Asplund, Carl, et al.
(författare)
-
1260 nm InGaAs vertical-cavity lasers
- 2002
-
Ingår i: Electronics Letters. - : Institution of Engineering and Technology (IET). - 0013-5194 .- 1350-911X. ; 38:13, s. 635-636
-
Tidskriftsartikel (refereegranskat)abstract
- The fabrication and performance of highly strained double-quantum well InGaAs/GaAs vertical-cavity lasers with record-long emission wavelength of 1260 nm at room temperature is reported. Depending on device diameter, the minimum threshold current is in the low mA-regime while the maximum output power exceeds 1 mW. The devices work continuous-wave over a wide temperature range of at least 10-120degrees C.
|
|
| 19. |
- Asplund, Maria. E., 1970, et al.
(författare)
-
Dynamics and fate of blue carbon in a mangrove-seagrass seascape : influence of landscape configuration and land-use change
- 2021
-
Ingår i: Landscape Ecology. - : Springer. - 0921-2973 .- 1572-9761. ; 36, s. 1489-1509
-
Tidskriftsartikel (refereegranskat)abstract
- Context Seagrass meadows act as efficient natural carbon sinks by sequestering atmospheric CO2 and through trapping of allochthonous organic material, thereby preserving organic carbon (C-org) in their sediments. Less understood is the influence of landscape configuration and transformation (land-use change) on carbon sequestration dynamics in coastal seascapes across the land-sea interface. Objectives We explored the influence of landscape configuration and degradation of adjacent mangroves on the dynamics and fate of C-org in seagrass habitats. Methods Through predictive modelling, we assessed sedimentary C-org content, stocks and source composition in multiple seascapes (km-wide buffer zones) dominated by different seagrass communities in northwest Madagascar. The study area encompassed seagrass meadows adjacent to intact and deforested mangroves. Results The sedimentary C-org content was influenced by a combination of landscape metrics and inherent habitat plant- and sediment-properties. We found a strong land-to-sea gradient, likely driven by hydrodynamic forces, generating distinct patterns in sedimentary C-org levels in seagrass seascapes. There was higher C-org content and a mangrove signal in seagrass surface sediments closer to the deforested mangrove area, possibly due to an escalated export of C-org from deforested mangrove soils. Seascapes comprising large continuous seagrass meadows had higher sedimentary C-org levels in comparison to more diverse and patchy seascapes. Conclusion Our results emphasize the benefit to consider the influence of seascape configuration and connectivity to accurately assess C-org content in coastal habitats. Understanding spatial patterns of variability and what is driving the observed patterns is useful for identifying carbon sink hotspots and develop management prioritizations.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Carlsson, Axel C., et al.
(författare)
-
Country of birth-specific and gender differences in prevalence of diabetes in Sweden
- 2013
-
Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 100:3, s. 404-408
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to investigate country or region of birth-specific prevalence and gender differences of diabetes in residents in Sweden, using Swedish-born men and women as referent. Methods: The Apolipoprotein MOrtality RISk (AMORIS) cohort was used (184,000 men and 151,453 women) aged between 20 and 80 years, with data from the CALAB laboratory, Stockholm, 1985-1996. Diabetes was defined as fasting glucose >= 7.0 mmol/L or a hospital diagnosis of diabetes. Country of birth was obtained by linkage to Swedish Censuses 1970-1990. Standardized prevalence rate ratios (SPRR) with 95% confidence intervals (95% CI) were estimated. Results: Five groups of women and one group of men had a significantly higher prevalence than Swedish-born (based on SPRR): women born in Iraq (6.0 (95% CI 1.3-28.9)), North Africa (6.9 (95% CI 3.1-15.3)), South Asia (3.1 (95% CI 1.0-10.0)), Syria (5.3 (95% CI 1.8-16.0)), Turkey (3.7 (95% CI 1.2-10.9)) and men born in other Middle Eastern countries (2.3 (95% CI 1.0-5.5)). Swedish-born men had a higher age-standardized prevalence of diabetes (3.9%) than Swedish born women ( 2.5%). A higher prevalence among men was also seen in other Western countries. In contrast, a higher age-standardized prevalence among women was observed in immigrants from Turkey (8.9% vs. 3.1%, p < 0.001), Syria (13.1% vs. 4.0%, p = 0.002), and North Africa (16.8% vs. 6.6%, p < 0.001). Conclusion: Female immigrants to Sweden from Iraq, North Africa, South Asia, Syria, and Turkey have an increased prevalence of diabetes of substantial public health concern.
|
|
