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- Keildson, Sarah, et al.
(författare)
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Expression of phosphofructokinase in skeletal muscle is influenced by genetic variation and associated with insulin sensitivity.
- 2014
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:3
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Tidskriftsartikel (refereegranskat)abstract
- Using an integrative approach in which genetic variation, gene expression, and clinical phenotypes are assessed in relevant tissues may help functionally characterize the contribution of genetics to disease susceptibility. We sought to identify genetic variation influencing skeletal muscle gene expression (expression quantitative trait loci [eQTLs]) as well as expression associated with measures of insulin sensitivity. We investigated associations of 3,799,401 genetic variants in expression of >7,000 genes from three cohorts (n = 104). We identified 287 genes with cis-acting eQTLs (false discovery rate [FDR] <5%; P < 1.96 × 10(-5)) and 49 expression-insulin sensitivity phenotype associations (i.e., fasting insulin, homeostasis model assessment-insulin resistance, and BMI) (FDR <5%; P = 1.34 × 10(-4)). One of these associations, fasting insulin/phosphofructokinase (PFKM), overlaps with an eQTL. Furthermore, the expression of PFKM, a rate-limiting enzyme in glycolysis, was nominally associated with glucose uptake in skeletal muscle (P = 0.026; n = 42) and overexpressed (Bonferroni-corrected P = 0.03) in skeletal muscle of patients with T2D (n = 102) compared with normoglycemic controls (n = 87). The PFKM eQTL (rs4547172; P = 7.69 × 10(-6)) was nominally associated with glucose uptake, glucose oxidation rate, intramuscular triglyceride content, and metabolic flexibility (P = 0.016-0.048; n = 178). We explored eQTL results using published data from genome-wide association studies (DIAGRAM and MAGIC), and a proxy for the PFKM eQTL (rs11168327; r(2) = 0.75) was nominally associated with T2D (DIAGRAM P = 2.7 × 10(-3)). Taken together, our analysis highlights PFKM as a potential regulator of skeletal muscle insulin sensitivity.
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- MARTIN-RINCON, M, et al.
(författare)
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Upregulation of nicotinamide n-methyltransferase in skeletal muscle following prolongedexercise and caloric restriction
- 2017
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Ingår i: 22nd Annual Congress of the European College of Sport Science. - Cologne, Germany : DTP Publishing. - 9783981841404 ; , s. 186-
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Konferensbidrag (refereegranskat)abstract
- IntroductionExpression of Nicotinamide (NA) N-methyltransferase (NNMT), the enzyme responsible for the methylation of NA to methylnicotinamide (MNA), is reduced in obese and diabetic mice. In rodent liver, NNMT activity and plasma MNA levels are increased after 90min of swimming.NNMT knockdown in mice white adipose tissue increases energy expenditure, suggesting a protective role against diet-induced obesity and type-2 diabetes. The role that NNMT plays in human metabolism remains unknown. Thus, the aims of the study were 1) to determine in human skeletal muscle (sm) whether NNMT is upregulated by prolonged exercise and 2) to ascertain whether the expression of NNMT in sm is influenced by severe energy deficit.MethodsFifteen overweight men underwent to 4 days of caloric restriction (CR) (0.8 g/kg BW/day) in combination with prolonged exercise (PE) (8h walking + 45min single-arm cranking/day). Three sm biopsies (exercised/non exercised arm and one leg) were obtained before (PRE), after (PE+CR) and following 3 days of control diet (isoenergetic) and reduced exercise (CD) to measure the expression of key metabolic genes (e.g. PDK4, CPT2, PFKFB3, NNMT) (microarray), NNMT protein expression (WB) and circulating plasma MNA levels (LC-MS). Maximal fat oxidation (MFO) (indirect calorimetry) and body composition (DEXA) were measured. ANOVA repeated-measures was used.ResultsDuring PE+CR the energy deficit was 5000 kcal/d reducing fat mass by 2.8 (PE+CR) and 3.8 kg (CD). MFO was increased. CPT2, PDK4, PFKFB3 genes (CHO-to-fat metabolic shift) were differentially expressed (FDR<5%) in at least one sm. Compared to PRE, after CD, NNMT gene expression was upregulated in all sm (~3-5 fold). Protein NNMT increased ~13-fold (p<0.001), ~9-fold (p<0.01) and ~5-fold (p<0.001) for non-exercised and exercised arm (45min/day) and leg (8h/day), respectively. Circulating levels of MNA were augmented two-fold. The increase in NNMT expression from PRE to CD was associated with the increase in MFO (r=0.37, p=0.01,n=45).DiscussionThis findings reveal that NNMT is upregulated in human sm in response to a severe energy deficit, with a simultaneous increase of MNA plasma levels. However, this response was attenuated in the exercised sm. NNMT may have a role in facilitating fat oxidation. Caloric restriction elicits increased sirtuins expression and activity, coupled with the NAD+ breakdown into NA. Overexpression of NNMT probably prevents accumulation of NA, which would otherwise inhibit the sirtuins. Our data suggest sm as a plausible source of MNA, which may act as a myokine with a role in the adaptation to starvation.
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- Müller, Dieter K, et al.
(författare)
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Tyska turister i Sverige : forskning och studier som ger ökad kunskap om tyska turister och som kan bidra till att svenska turistföretag blir framgångsrika på den tyska resemarknaden
- 2001
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Boken "Tyska turister i Sverige" syftar till att öka kunskapen om tysk turism i Sverige - i ett historiskt perspektiv och i ett nutidsperspektiv. Ambitionen är inte att ge en helhetsbild. I stället inriktar sig boken på ett antal områden där ETOURs forskning i större eller mindre omfattning haft fokus på tysk turism. Det gäller fjällturism, fritidshusturism, miljöturism samt charterturism till norra Sverige. Detta kompletterat med färska studier bland tyska researrangörer och konsumenter samt en allmän bakgrund till tyskar och dess resande hoppas vi ska ge en värdefull bild av "Tyska turister i Sverige". Förhoppningen är också att den forskning och de studier som finns i boken mer allmänt ska kunna bidra till att öka kunskapen hos svenska turistföretag för att de ska bli framgångsrika på olika resemarknader. Dieter K. Müller, tidigare verksam vid ETOUR, nu lektor vid Umeå universitet, tar i de inledande avsnitten upp mer allmänna aspekter , t.ex. om tyskars syn på Sverige, varför just tyskar reser mest i världen och varför många tyskar väljer Sverige som turistmål. Dieter skriver i nästa kapitel om tyskarnas intresse för svenska fritidshus. Nästa kapitel handlar om de tyskägda stugorna i Norrland, skrivet av Robert Pettersson vid ETOUR. Den tyska fjällturisten är rubriken på ett avsnitt av Peter Fredman och Christine Lundberg, båda verksamma på ETOUR. Bodil Frey är författare till det avsnitt som handlar om de tyska gäster som kommer till vårt land enbart för att uppleva naturen. Interjuver av tyska researrangörer och konsumenter redovisas i de två avslutande avsnitten i boken. Flera av bokens kapitel avslutas med tips och slutsatser som kan vara till nytta för turistföretagare i deras strävan att bli framgångsrika på den tyska utresemarknaden.
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- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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