| 1. |
- Axfors, Cathrine, et al.
(författare)
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Cohort profile : the Biology, Affect, Stress, Imaging and Cognition (BASIC) study on perinatal depression in a population-based Swedish cohort
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: With the population-based, prospective Biology, Affect, Stress, Imaging and Cognition (BASIC) cohort, we aim to investigate the biopsychosocial aetiological processes involved in perinatal depression (PND) and to pinpoint its predictors in order to improve early detection.PARTICIPANTS: From September 2009 to November 2018, the BASIC study at Uppsala University Hospital, Sweden, has enrolled 5492 women, in 6478 pregnancies, of which 46.3% first-time pregnancies and with an average age of 31.5 years. After inclusion around gestational week 16-18, participants are followed-up with data collection points around gestational week 32, at childbirth, as well as three times postpartum: after 6 weeks, 6 months and 1 year. At the last follow-up, 70.8% still remain in the cohort.FINDINGS TO DATE: In addition to internet-based surveys with self-report instruments, participants contribute with biological samples, for example, blood samples (maternal and from umbilical cord), biopsies (umbilical cord and placenta) and microbiota samples. A nested case-control subsample also takes part in cognitive and emotional tests, heart rate variability tests and bioimpedance tests. Subprojects have identified various correlates of PND of psychological and obstetric origin in addition to factors of the hypothalamic-pituitary-adrenal axis and immune system.FUTURE PLANS: In parallel with the completion of data collection (final follow-up November 2019), BASIC study data are currently analysed in multiple subprojects. Since 2012, we are conducting an ongoing follow-up study on the participants and their children up to 6 years of age (U-BIRTH). Researchers interested in collaboration may contact Professor Alkistis Skalkidou (corresponding author) with their request to be considered by the BASIC study steering committee.
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| 2. |
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| 3. |
- Amsteus, Martin, 1972-, et al.
(författare)
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The Sound of Choice
- 2016
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Ingår i: International Journal of Business and Social Science. - : Center for Promoting Ideas. - 2219-1933. ; 7:1, s. 42-49
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to testthe effect of suggestive music on consumer choice in cafés. It is proposed that suggestive music influences consumer choice in cafés. The hypotheses were tested through Chi-square on a totalof 283 measures. The results show that suggestive music has an effect on consumer choice in cafés. Managers who want to influence consumer choice in cafés through suggestive music may be able to do so. The results provide empirical support for the idea that suggestive music and the associations it carries represent information that consumers use for assessing choices and making selections.
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| 4. |
- Efe, C., et al.
(författare)
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Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis
- 2019
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 114:7, s. 1101-1108
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.
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| 5. |
- Henriks, Göran, et al.
(författare)
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Skapa en kultur med patienten som en aktiv partner
- 2015
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Ingår i: Kvalitetsmässan 2015, 3-5 november 2015, Göteborg, Sverige..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Utgångspunkten i personcentrerad vård är att utgå från att alla människor som arbetar inom vård och omsorg är kapabla att ta ansvar för sig själva och sitt arbete. Men hur styr man en verksamhet som drivs av berättelser, lyssnande, överenskommelser och dokumentationer? Är det styrning underifrån, ovanifrån eller genom partnerskap? Det är en utmaning att leda en verksamhet som involverar patienten som aktiv partner och en del av vårdteamet.
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| 6. |
- Henriksson, Emma, et al.
(författare)
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SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes
- 2015
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 128:3, s. 472-486
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Tidskriftsartikel (refereegranskat)abstract
- Salt-inducible kinase 2 (SIK2) is an AMP-activated protein kinase (AMPK) related kinase abundantly expressed in adipose tissue. Our aim was to identify molecular targets and functions of SIK2 in adipocytes, and to address the role of PKA-mediated phosphorylation of SIK2 on Ser358. Modulation of SIK2 in adipocytes resulted in altered phosphorylation of CREB-regulated transcription co-activator 2 (CRTC2), CRTC3 and class IIa histone deacetylase 4 (HDAC4). Furthermore, CRTC2, CRTC3, HDAC4 and protein phosphatase 2A (PP2A) interacted with SIK2, and the binding of CRTCs and PP2A to wild-type but not Ser358Ala SIK2, was reduced by cAMP elevation. Silencing of SIK2 resulted in reduced GLUT4 (also known as SLC2A4) protein levels, whereas cells treated with CRTC2 or HDAC4 siRNA displayed increased levels of GLUT4. Overexpression or pharmacological inhibition of SIK2 resulted in increased and decreased glucose uptake, respectively. We also describe a SIK2-CRTC2-HDAC4 pathway and its regulation in human adipocytes, strengthening the physiological relevance of our findings. Collectively, we demonstrate that SIK2 acts directly on CRTC2, CRTC3 and HDAC4, and that the cAMP-PKA pathway reduces the interaction of SIK2 with CRTCs and PP2A. Downstream, SIK2 increases GLUT4 levels and glucose uptake in adipocytes.
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| 7. |
- Henriksson, Hanna E., et al.
(författare)
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Blood plasma metabolic profiling of pregnant women with antenatal depressive symptoms
- 2019
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Antenatal depression affects similar to 9-19% of pregnant women and can exert persistent adverse effects on both mother and child. There is a need for a deeper understanding of antenatal depression mechanisms and the development of tools for reliable diagnosis and early identification of women at high risk. As the use of untargeted blood metabolomics in the investigation of psychiatric and neurological diseases has increased substantially, the main objective of this study was to investigate whether untargeted gas chromatography-mass spectrometry (GC-MS) plasma metabolomics in 45 women in late pregnancy, residing in Uppsala, Sweden, could indicate metabolic differences between women with and without depressive symptoms. Furthermore, seasonal differences in the metabolic profiles were explored. When comparing the profiles of cases with controls, independently of season, no differences were observed. However, seasonal differences were observed in the metabolic profiles of control samples, suggesting a favorable cardiometabolic profile in the summer vs. winter, as indicated by lower glucose and sugar acid concentrations and lactate to pyruvate ratio, and higher abundance of arginine and phosphate. Similar differences were identified between cases and controls among summer pregnancies, indicating an association between a stressed metabolism and depressive symptoms. No depression-specific differences were apparent among depressed and non-depressed women, in the winter pregnancies; this could be attributed to an already stressed metabolism due to the winter living conditions. Our results provide new insights into the pathophysiology of antenatal depression, and warrant further investigation of the use of metabolomics in antenatal depression in larger cohorts.
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| 8. |
- Henriksson, Hanna E., et al.
(författare)
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Spring peaks and autumn troughs identified in peripheral inflammatory markers during the peripartum period
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 15328-
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Tidskriftsartikel (refereegranskat)abstract
- Seasonal variations have recently been described in biomarkers, cell types, and gene expression associated with the immune system, but so far no studies have been conducted among women in the peripartum period. It is of note that pregnancy complications and outcomes, as well as autoimmune diseases, have also been reported to exhibit seasonal fluctuations. We report here a clear-cut seasonal pattern of 23 inflammatory markers, analysed using proximity-extension assay technology, in pregnant women. The inflammatory markers generally peaked in the spring and had a trough in the autumn. During the postpartum period we found seasonality in one inflammatory marker, namely monocyte chemotactic protein 4 (MCP-4). Our findings suggest that seasonal variations in peripheral inflammatory markers are only observed during pregnancy. The results of this study could be valuable to professionals working within the field of immunology-related areas, and provide insight for the understanding of obstetric complications.
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| 9. |
- Henriksson, Jessica, 1987-, et al.
(författare)
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Effects of Eight-Week-Web-Based Mindfulness Training on Pain Intensity, Pain Acceptance, and Life Satisfaction in Individuals With Chronic Pain
- 2016
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Ingår i: Psychological Reports. - : Sage Publications. - 0033-2941 .- 1558-691X. ; 119:3, s. 586-607
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Tidskriftsartikel (refereegranskat)abstract
- This study examined the effects of an eight-week-web-based mindfulness programdesigned for individuals with chronic pain. A sample of 107 participants with chronicpain (M¼51.0 years, SD¼9.3) were randomly assigned to a treatment group and acontrol group. The mindfulness program involved 20 minutes of training per day, sixdays a week, for eight weeks. During this period, the control group was invited to anonline discussion forum involving pain-related topics. A total of 77 participantscompleted the postintervention assessment (n¼36 in the treatment group, n¼41in the control group). The group assigned to mindfulness training showed increasedmindfulness skills (Cohen’s d¼1.18), reduced pain intensity (d¼0.47–0.82), reducedpain-related interference/suffering (d¼0.39–0.85), heightened pain acceptance(d¼0.66), reduced affective distress (d¼0.67), and higher ratings of life satisfaction(d¼0.54) following the training with no or minor changes up for the control group(d values 0.01–0.23), a pattern substantiated by significant group-by-time interactions.Despite limitations of this study, including a less than ideal control groupto isolate effects of mindfulness and lack of a long-term follow-up, the results appearpromising and may motivate further investigations.
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| 10. |
- Henriksson, Malin, 1981-, et al.
(författare)
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"Om nåt skulle hända" : Ett gestaltningsprojekt om ungas upplevelser av otrygghet i utemiljöer
- 2016
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Rapport (populärvet., debatt m.m.)abstract
- Under 2016 producerade Statens väg- och transportforskningsinstitut (VTI) tillsammans med Östergötlands museum en vandringsutställning om ungas upplevelser av otrygghet. Projektet finansierades av Boverket inom utlysningen ”stöd till utvecklingsprojekt för jämställda offentliga miljöer i städer och tätorter”. Projektet utgår från problematiken att ungdomars upplevelser av otrygghet sällan kommer till uttryck i stadsplaneringen. Inte heller i forskningen om upplevelser av våld och otrygghet i det offentliga rummet uppmärksammas ungdomar i särskilt hög grad. Samtidigt förflyttar sig ungdomar som grupp mer än andra grupper och vistas i högre grad utomhus. De är också utomhus på andra tidpunkter än vuxna, på kvällen och natten. Vidare är ungdomar, oavsett kön, mer utsatta för våld utomhus än andra grupper. Det är därför att utveckla nya verktyg för att belysa ungdomars erfarenheter av otrygghet i utomhusmiljöer.Underlaget för utställningen utgjordes av gruppintervjuer med ett fyrtiotal ungdomar (killar, tjejer och transpersoner) mellan 13 och 20 år. Den feministiska metoden minnesarbete användes för att underlätta samtal om trygghet, otrygghet och rädsla. Metoden går ut på att deltagarna i en grupp skriver individuella minnen på ett på förhand bestämt tema. Minnena tolkas sedan kollektivt i gruppen.Intervjuerna tolkades och bearbetades av projektgruppen. Utifrån tolkningsprocessen gestaltades ungdomarnas erfarenheter dels fotografiskt och dels i text. Fyra fiktiva karaktärer togs fram och i utställningen får besökaren följa dem hem. Milo, David, Jo och Semira har alla olika erfarenheter och upplever olika moment i staden och hemresan som otrygga. Vidare togs en pedagogisk handledning fram. Den pedagogiska handledningen innehåller förslag på övningar som fördjupar utställningens teman. Den fungerar som ett stöd för skolor som hyr utställningen och kan användas av lärare i undervisningen. Pedagoger från Östergötlands museum kan vidare leda lektioner som bygger på handledningen om skolan så önskar.Projektet avslutades med en fyra veckor lång turné där ungdomar i olika åldrar fick ta del av utställningen och arbeta med den pedagogiskt. Turnén utvärderades med genomgående goda resultat.Projektet bidrar avslutningsvis till att stärka planeringen av jämställda miljöer på två sätt. För det första ger utställningen insikter om hur unga människor upplever trygghet i utemiljöer. För det andra är utställningen ett verktyg som gör det möjligt att praktiskt arbeta med frågorna pedagogiskt i skolmiljöer, eller i stadsplaneringssammanhang med planerare och andra aktörer.
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| 11. |
- Karimi, Masoud, et al.
(författare)
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A retrospective study of extracolonic, non-endometrial cancer in Swedish Lynch syndrome families
- 2018
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Ingår i: Hereditary Cancer in Clinical Practice. - : BMC. - 1731-2302 .- 1897-4287. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. Carriers are predisposed to colorectal and endometrial cancer, but also other cancer types. The purpose of this retrospective study was to characterize the tumour spectrum of the Swedish Lynch syndrome families.MethodsData were obtained from genetically verified 235 Lynch families from five of the six health care regions in Sweden. The material was stratified for gender, primary cancer, age and mutated gene and the relative proportions of specific cancer types were compared to those in the general population.ResultsA total of 1053 family members had 1493 cancer diagnoses of which 1011 were colorectal or endometrial cancer. Individuals with pathogenic variants in MLH1 and MSH2 comprised 78% of the cohort. Among the 482 non-colorectal/non-endometrial cancer diagnoses, MSH2 carriers demonstrated a significantly increased proportion of urinary tract, gastric, small bowel, ovarian and non-melanoma skin cancer compared to the normal population. MLH1 carriers had an elevated proportion of gastrointestinal cancers (gastric, small bowel, pancreas), while MSH6 carriers had more ovarian cancer than expected. Gastric cancer was predominantly noted in older generations.ConclusionLynch syndrome confers an increased risk for multiple cancers other than colorectal and endometrial cancer. The proportions of other cancers vary between different MMR genes, with highest frequency in MSH2-carriers. Gender and age also affect the tumour spectrum, demonstrating the importance of additional environmental and constitutional parameters in determining the predisposition for different cancer types.
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| 12. |
- Karimi, Masoud, et al.
(författare)
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A retrospective study of extracolonic, non-endometrial cancer in Swedish Lynch syndrome families 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis 11 Medical and Health Sciences 1117 Public Health and Health Services
- 2018
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Ingår i: Hereditary Cancer in Clinical Practice. - : Springer Science and Business Media LLC. - 1731-2302 .- 1897-4287. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. Carriers are predisposed to colorectal and endometrial cancer, but also other cancer types. The purpose of this retrospective study was to characterize the tumour spectrum of the Swedish Lynch syndrome families. Methods: Data were obtained from genetically verified 235 Lynch families from five of the six health care regions in Sweden. The material was stratified for gender, primary cancer, age and mutated gene and the relative proportions of specific cancer types were compared to those in the general population. Results: A total of 1053 family members had 1493 cancer diagnoses of which 1011 were colorectal or endometrial cancer. Individuals with pathogenic variants in MLH1 and MSH2 comprised 78% of the cohort. Among the 482 non-colorectal/non-endometrial cancer diagnoses, MSH2 carriers demonstrated a significantly increased proportion of urinary tract, gastric, small bowel, ovarian and non-melanoma skin cancer compared to the normal population. MLH1 carriers had an elevated proportion of gastrointestinal cancers (gastric, small bowel, pancreas), while MSH6 carriers had more ovarian cancer than expected. Gastric cancer was predominantly noted in older generations. Conclusion: Lynch syndrome confers an increased risk for multiple cancers other than colorectal and endometrial cancer. The proportions of other cancers vary between different MMR genes, with highest frequency in MSH2-carriers. Gender and age also affect the tumour spectrum, demonstrating the importance of additional environmental and constitutional parameters in determining the predisposition for different cancer types.
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| 13. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 14. |
- Kjellén, Emma, 1984, et al.
(författare)
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Aphasia and literacy - the insider's perspective
- 2017
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Ingår i: International Journal of Language and Communication Disorders. - : Wiley. - 1368-2822 .- 1460-6984. ; 52:5, s. 573-584
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 The Authors International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.Background: Few studies have investigated how people with aphasia (PWA) experience literacy skills. Taking the insider's perspective is a way to increase understanding of the individual experiences of literacy among PWA, which may have clinical implications. Aims: To describe how literacy, i.e., reading and writing, is experienced in everyday life by PWA and to gain insight into the part played by literacy skills in their lives. Methods & Procedures: A qualitative descriptive research approach was taken. In-depth interviews were conducted with 12 PWA (six women and six men) who had all lived with aphasia for at least 6 months post-stroke. The interviews were analysed using qualitative content analysis. Outcomes & Results: One overarching theme emerged from the data: literacy as an ongoing recovery process. Based on this overarching theme, two subthemes were identified: changes in conditions for literacy (experiences of reading and writing initially post-onset compared with experiences at the time of the interview); and facing expectations about literacy (participants' own and other people's expectations of them in terms of literacy). Conclusions & Implications: The findings are important at a general level in that they indicate that PWA are able to articulate their individual experiences and thoughts about literacy, i.e., reading and writing. Specifically, PWA in this study experience literacy as playing an essential part in their lives and the findings imply that personal experiences are important in the design of reading and writing interventions in speech and language therapy.
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| 15. |
- Ladds, Marcus J. G. W., et al.
(författare)
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A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.
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| 16. |
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| 17. |
- Roberts, Neil A., et al.
(författare)
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Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder
- 2019
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Ingår i: Kidney International. - : ELSEVIER SCIENCE INC. - 0085-2538 .- 1523-1755. ; 95:5, s. 1138-1152
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in leucine-rich-repeats and immunoglobulin-likedomains 2 (LRIG2) or in heparanase 2 (HPSE2) cause urofacial syndrome, a devastating autosomal recessive disease of functional bladder outlet obstruction. It has been speculated that urofacial syndrome has a neural basis, but it is unknown whether defects in urinary bladder innervation are present. We hypothesized that urofacial syndrome features a peripheral neuropathy of the bladder. Mice with homozygous targeted Lrig2 mutations had urinary defects resembling those found in urofacial syndrome. There was no anatomical blockage of the outflow tract, consistent with a functional bladder outlet obstruction. Transcriptome analysis revealed differential expression of 12 known transcripts in addition to Lrig2, including 8 with established roles in neurobiology. Mice with homozygous mutations in either Lrig2 or Hpse2 had increased nerve density within the body of the urinary bladder and decreased nerve density around the urinary outflow tract. In a sample of 155 children with chronic kidney disease and urinary symptoms, we discovered novel homozygous missense LRIG2 variants that were predicted to be pathogenic in 2 individuals with non-syndromic bladder outlet obstruction. These observations provide evidence that a peripheral neuropathy is central to the pathobiology of functional bladder outlet obstruction in urofacial syndrome, and emphasize the importance of LRIG2 and heparanase 2 for nerve patterning in the urinary tract.
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| 18. |
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| 19. |
- Svennberg, Emma, et al.
(författare)
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N-terminal pro B-type natriuretic peptide in systematic screening for atrial fibrillation
- 2017
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 103:16, s. 1271-1277
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Tidskriftsartikel (refereegranskat)abstract
- Objective Screening for atrial fibrillation (AF) in individuals aged 65 and above is recommended by the European Society of Cardiology. Increased levels of the biomarker N-terminal pro B-type natriuretic peptide (NT-proBNP) has in cohort studies been associated with incident AF. The aim of this study was to assess whether NT-proBNP could be useful for AF detection in systematic screening.Methods The Strokestop study entailed 7173 Swedish residents aged 75/76 that were screened for AF using twice daily intermittent ECG recordings during 2 weeks. In a substudy of 886 participants, the last 815 consecutive participants and 71 individuals with newly detected AF, levels of NT-proBNP were determined.Results Participants with newly detected AF (n=96) had a median NT-proBNP of 330 ng/L (IQR 121; 634). In individuals without AF (n=742), median NT-proBNP was 171 ng/L (IQR 95; 283), p<0.001. The CHA2DS2-VASc parameters did not differ significantly between individuals with newly detected AF and without AF nor between newly detected AF in the NT-proBNP cohort compared with the cohort where NT-proBNP was not assessed. Using an NT-proBNP cut-off of >= 125 ng/L in a non-acute setting yielded a negative predictive value of 92%, meaning that 35% fewer participants would need to be screened when applied to systematic AF screening. Adding weight to NT-proBNP further reduced participants needed to be screened with a preserved sensitivity.Conclusions NT-proBNP was increased in individuals with newly detected AF. Prospective studies could clarify if NT-proBNP can be used to correctly select individuals that benefit most from AF screening.
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| 20. |
- Säll, Johanna, et al.
(författare)
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Salt-inducible kinase 2 and -3 are downregulated in adipose tissue from obese or insulin-resistant individuals : implications for insulin signalling and glucose uptake in human adipocytes
- 2017
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 60:2, s. 314-323
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Salt-inducible kinases (SIKs) are related to the metabolic regulator AMP-activated protein kinase (AMPK). SIK2 is abundant in adipose tissue. The aims of this study were to investigate the expression of SIKs in relation to human obesity and insulin resistance, and to evaluate whether changes in the expression of SIKs might play a causal role in the development of disturbed glucose uptake in human adipocytes.METHODS: SIK mRNA and protein was determined in human adipose tissue or adipocytes, and correlated to clinical variables. SIK2 and SIK3 expression and phosphorylation were analysed in adipocytes treated with TNF-α. Glucose uptake, GLUT protein levels and localisation, phosphorylation of protein kinase B (PKB/Akt) and the SIK substrate histone deacetylase 4 (HDAC4) were analysed after the SIKs had been silenced using small interfering RNA (siRNA) or inhibited using a pan-SIK-inhibitor (HG-9-91-01).RESULTS: We demonstrate that SIK2 and SIK3 mRNA are downregulated in adipose tissue from obese individuals and that the expression is regulated by weight change. SIK2 is also negatively associated with in vivo insulin resistance (HOMA-IR), independently of BMI and age. Moreover, SIK2 protein levels and specific kinase activity display a negative correlation to BMI in human adipocytes. Furthermore, SIK2 and SIK3 are downregulated by TNF-α in adipocytes. Silencing or inhibiting SIK1-3 in adipocytes results in reduced phosphorylation of HDAC4 and PKB/Akt, less GLUT4 at the plasma membrane, and lower basal and insulin-stimulated glucose uptake in adipocytes.CONCLUSION/INTERPRETATION: This is the first study to describe the expression and function of SIKs in human adipocytes. Our data suggest that SIKs might be protective in the development of obesity-induced insulin resistance, with implications for future treatment strategies.
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