| 1. |
- Andersson, Sara, et al.
(författare)
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Rehabilitering
- 2007
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Ingår i: Nordisk lärobok i audiologi. - Bromma : C. A. Tegnér AB. - 9789163194405 ; , s. 325-389
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Sjukdomstillstånd och skador i organ och vävnader orsakar diverse funktionella avvikelser, som i sin tur ger upphov till symptom, som personen ifråga kan iaktta och lida av. Dessa orsakar funktionsnedsättningar, som påverkar individens möjligheter att fungera och klara sig i sin dagliga miljö hemma, i olika arbetssituationer och i olika sociala sammanhang.
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| 2. |
- Danielsson, Anna, et al.
(författare)
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Attenuation of insulin-stimulated insulin receptor substrate-1 serine 307 phosphorylation in insulin resistance of type 2 diabetes
- 2005
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Ingår i: Journal of biological chemistry. - 0021-9258 .- 1083-351X. ; 280:41, s. 34389-3492
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance is a primary characteristic of type 2 diabetes and likely causally related to the pathogenesis of the disease. It is a result of defects in signal transduction from the cell surface receptor of insulin to target effects. We found that insulin-stimulated phosphorylation of serine 307 (corresponding to serine 302 in the murine sequence) in the immediate downstream mediator protein of the insulin receptor, insulin receptor substrate-1 (IRS1), is required for efficient insulin signaling and that this phosphorylation is attenuated in adipocytes from patients with type 2 diabetes. Inhibition of serine 307 phosphorylation by rapamycin mimicked type 2 diabetes and reduced the sensitivity of IRS1 tyrosine phosphorylation in response to insulin, while stimulation of the phosphorylation by okadaic acid, in cells from patients with type 2 diabetes, rescued cells from insulin resistance. EC50 for insulin-stimulated phosphorylation of serine 307 was about 0.2 nM with a t1/2 of about 2 min. The amount of IRS1 was similar in cells from non-diabetic and diabetic subjects. These findings identify a molecular mechanism for insulin resistance in non-selected patients with type 2 diabetes.
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| 3. |
- Danielsson, Anna, et al.
(författare)
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Insulin resistance in human adipocytes occurs downstream of IRS1 after surgical cell isolation but at the level of phosphorylation of IRS1 in type 2 diabetes
- 2005
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 272:1, s. 141-151
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance is a cardinal feature of type 2 diabetes and also a consequence of trauma such as surgery. Directly after surgery and cell isolation, adipocytes were insulin resistant, but this was reversed after overnight incubation in 10% CO2 at 37 °C. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)1 was insulin sensitive, but protein kinase B (PKB) and downstream metabolic effects exhibited insulin resistance that was reversed by overnight incubation. MAP-kinases ERK1/2 and p38 were strongly phosphorylated after surgery, but was dephosphorylated during reversal of insulin resistance. Phosphorylation of MAP-kinase was not caused by collagenase treatment during cell isolation and was present also in tissue pieces that were not subjected to cell isolation procedures. The insulin resistance directly after surgery and cell isolation was different from insulin resistance of type 2 diabetes; adipocytes from patients with type 2 diabetes remained insulin resistant after overnight incubation. IRS1, PKB, and downstream metabolic effects, but not insulin-stimulated tyrosine phosphorylation of insulin receptor, exhibited insulin resistance. These findings suggest a new approach in the study of surgery-induced insulin resistance and indicate that human adipocytes should recover after surgical procedures for analysis of insulin signalling. Moreover, we pinpoint the signalling dysregulation in type 2 diabetes to be the insulin-stimulated phosphorylation of IRS1 in human adipocytes.
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| 4. |
- Danielsson, Anna, et al.
(författare)
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Short-Term Overeating Induces Insulin Resistance in Fat Cells in Lean Human Subjects
- 2009
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Ingår i: Molecular Medicine. - : Springer Science and Business Media LLC. - 1076-1551 .- 1528-3658. ; 15:7-8, s. 228-234
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance and type 2 diabetes (T2D) are closely linked to obesity. Numerous prospective studies have reported on weight gain, insulin resistance, and insulin signaling in experimental animals, but not in humans. We examined insulin signaling in adipocytes from lean volunteers, before and at the end of a 4-wk period of consuming a fast-food, high-calorie diet that led to weight gain. We also examined adipocytes from patients with T2D. During the high-calorie diet, subjects gained 10% body weight and 19% total body fat, but stayed lean (body mass index = 24.3 kg/m2) and developed moderate systemic insulin resistance. Similarly to the situation in T2D subjects, in subjects on the high-calorie diet, the amount of insulin receptors was reduced and phosphorylation of IRS1 at tyrosine and at serine-307 (human sequence, corresponding to murine serine-302) were impaired. The amount of insulin receptor substrate protein-1 (IRS1) and the phosphorylation of IRS1 at serine-312 (human sequence, corresponding to murine serine-307) were unaffected by the diet. Unlike the T2D subjects, in subjects on the high-calorie diet, likely owing to the ongoing weight-gain, phosphorylation of MAP-kinases ERK1/2 became hyperresponsive to insulin. To our knowledge this study is the first to investigate insulin signaling during overeating in humans, and it demonstrates that T2D effects on intracellular insulin signaling already occur after 4 wks of a high-calorie diet and that the effects in humans differ from those in laboratory animals.
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| 5. |
- Johansson, Ann-Sofi, et al.
(författare)
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Attenuated amyloid-β aggregation and neurotoxicity owing to methionine oxidation
- 2007
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Ingår i: NeuroReport. - 0959-4965 .- 1473-558X. ; 18:6, s. 559-563
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Tidskriftsartikel (refereegranskat)abstract
- Aggregation of the amyloid-beta (Abeta) peptide into amyloid plaques is a characteristic feature of Alzheimer's disease neuropathogenesis. We and others have previously demonstrated delayed Abeta aggregation as a consequence of oxidizing a single methionine residue at position 35 (Met-35). Here, we examined the consequences of Met-35 oxidation on the extremely aggregation-prone peptides Abeta1-42 and Abeta1-40Arctic with respect to protofibril and oligomer formation as well as neurotoxicity. Size exclusion chromatography and mass spectrometry demonstrated that monomer/dimers prevailed over larger oligomers after oxidizing Met-35, and consequently protofibril formation and aggregation of both Abeta1-42 and Abeta1-40Arctic were delayed. The oxidized peptides completely lacked neurotoxic effects in cortical neuronal cultures under these conditions, in contrast to the neurotoxic properties of the unoxidized peptides. We conclude that oxidation of Met-35 significantly attenuates aggregation of Abeta1-42 and Abeta1-40Arctic, and thereby reduces neurotoxicity.
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| 6. |
- Kostela, Johan, Doktor i Fysikalisk kemi, 1975-, et al.
(författare)
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Från ord till handling : Metoder för att omsätta miljömål till praktisk handling
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Ett flertal av dagens stora miljöproblem är betingade av människors livsstil. Samtidigt har dålig miljö ofta en negativ inverkan på människors hälsa. Att påverka människors beteende är nödvändigt för att åstadkomma en bättre miljö och ett förbättrat hälsotillstånd. Detta kan ske genom utbildning och information, men frågan är på vilket sätt detta ska ske för att verkligen ge avtryck i människors beteende. I handlingsplanen för Dalarnas Miljömål finns flera åtgärder som innebär informationsinsatser inom områden som berör sambandet mellan miljö och hälsa. Här finns också starka kopplingar till flera av de elva folkhälsomålen. Dalarnas Miljömål är ett måldokument med relativt hög abstraktionsnivå. Nästa steg är att operationalisera det – att gå från ord till handling. Det finns ett stort behov av att hitta metoder att kommunicera miljömålen med olika väl avgränsade målgrupper. Detta projekt har handlat om att pröva olika metoder för detta och bygger på några grundläggande pedagogiska teorier som kan sammanfattas med begreppen delaktighet och motivation. Projektet har också visat hur övergripande måldokument med fördel kan omsättas i praktiken genom att bygga nedifrån och börja i det lilla. Vad som påverkar en människas beteende styrs av en rad skilda faktorer som varierar från människa till människa, från sakområde till sakområde och som även förändras över tid. En gemensam nämnare är att det förändrade beteendet ger någon form av vinst för den enskilda människan i form av till exempel förbättrad hälsa, ekonomi eller en bättre miljö. Vinsterna för den enskilde behöver inte nödvändigtvis vara direkt kopplade till miljömålen utan kan vara indirekta som t ex önskan att tillhöra ett avantgarde, att bli omtyckt av andra etc. Det viktigaste för varje individ är att frågan ”What’s in it for me?” får ett nöjaktigt svar. Det kräver en tydlig och avgränsad målgrupp vilket är en viktig utgångspunkt i detta projekt.
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| 7. |
- Öst, Anita, 1965-, et al.
(författare)
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Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes
- 2007
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Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860. ; 21:13, s. 3696-3704
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Tidskriftsartikel (refereegranskat)abstract
- Reduced sensitivity to insulin in adipose, muscle, and liver tissues is a hallmark of type 2 diabetes. Animal models and patients with type 2 diabetes exhibit elevated levels of circulating retinol-binding protein (RBP4), and RBP4 can induce insulin resistance in mice. However, little is known about how RBP4 affects insulin signaling. We examined the mechanisms of action of RBP4 in primary human adipocytes. RBP4-treated adipocytes exhibited the same molecular defects in insulin signaling, via IRS1 to MAP kinase, as in adipocytes from patients with type 2 diabetes. Without affecting autophosphorylation of the insulin receptor, RBP4 blocked the insulin-stimulated phosphorylation of IRS1 at serine (307) [corresponding to serine (302) in the murine sequence] and concomitantly increased the EC50 (from 0.5 to 2 nM) for insulin stimulation of IRS1 phosphorylation at tyrosine. The phosphorylation of IRS1 at serine (312) [corresponding to serine (307) in the murine sequence] was not affected in cells from diabetic patients and was also not affected by RBP4. The EC50 for insulin stimulation of downstream phosphorylation of MAP kinase ERK1/2 was increased (from 0.2 to 0.8 nM) by RBP4. We show that ERK1/2 phosphorylation is similarly impaired in adipocytes from patients with type 2 diabetes. However, the sensitivity to insulin for downstream signaling to control of protein kinase B and glucose uptake was not affected by RBP4. When insulin-resistant adipocytes from patients with type 2 diabetes were incubated with antibodies against RBP4, insulin-induced phosphorylation of IRS1 at serine (307) was normalized and the EC50 for insulin stimulation of ERK1/2 phosphorylation was reduced. Endogenous levels of RBP4 were markedly reduced in adipocytes from obese or type 2 diabetic subjects, whereas expression levels of RBP4 mRNA were unaffected. These findings indicate that RBP4 may be released from diabetic adipocytes and act locally to inhibit phosphorylation of IRS1 at serine (307), a phosphorylation site that may integrate nutrient sensing with insulin signaling.
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