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- Andersson, Christian X, 1973, et al.
(författare)
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Inflamed adipose tissue, insulin resistance and vascular injury
- 2008
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Ingår i: Diabetes/Metabolism Research and Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 24:8, s. 595-603
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is the most common metabolic disorder today and has reached epidemic proportions in many countries. Insulin resistance and inflammation play a central role in the pathogenesis of type 2 diabetes and are present long before the onset of the disease. During this time, many of the complications associated with type 2 diabetes are initiated. Of major concern is the two- to fourfold increase in cardiovascular morbidity and mortality in this group compared to a nondiabetic population. Obesity, characterized by enlarged fat cells, and insulin resistance are, like type 2 diabetes, associated with impaired adipogenesis and a low-grade chronic inflammation that to a large extent emanates from the adipose tissue. Both these processes contribute to unfavourable alterations of the circulating levels of several bioactive molecules (adipokines) that are secreted from the adipose tissue, many of which have documented inhibitory effects on insulin sensitivity in the liver and peripheral tissues and, in addition, have negative effects on the cardiovascular system.Here we review current knowledge of the adipose tissue as an endocrine organ, the local and systemic effects of a chronic state of low-grade inflammation residing in the adipose tissue, and, in particular, the effects of inflammation and circulating adipokines on the vascular wall.
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| 2. |
- Andersson, Christian X, 1973, et al.
(författare)
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Insulin antagonizes interleukin-6 signaling and is anti-inflammatory in 3T3-L1 adipocytes
- 2007
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Ingår i: J Biol Chem. - 0021-9258. ; 282:13, s. 9430-5
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Tidskriftsartikel (refereegranskat)abstract
- Adipose tissue secretes different adipokines, including interleukin-6 (IL-6), that have been implicated in the insulin resistance and inflammatory state characterizing obesity. We examined the putative cross-talk between insulin and IL-6 in adipose cells and found that insulin exerts an inhibitory effect on the IL-6 signaling pathway by altering the post-translational modifications of the signal transducer and activator of transcription 3 (STAT3). Insulin reduces the tyrosine phosphorylation and increases the serine phosphorylation of STAT3, thereby reducing its nuclear localization and transcriptional activity. Signaling through the MEK/MAPK pathway plays an important role as treatment with the MEK inhibitor PD98059 reduces the effects of insulin on IL-6 signaling. We also show that the protein tyrosine phosphatase SHP2 is activated upon insulin signaling and is required for the dephosphorylation of STAT3 and that insulin exerts a synergistic effect with IL-6 on suppressor of cytokine signaling 3 expression. As a consequence, the IL-6-induced expression of the inflammatory markers serum amyloid A 3 and haptoglobin are significantly decreased in cells incubated with both IL-6 and insulin. Thus, insulin exerts an important anti-inflammatory effect in adipose cells by impairing the IL-6 signal at several levels.
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| 3. |
- Andersson, Patrik, 1974, et al.
(författare)
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Framtidsbilder för samhällsbyggnad
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Framtidsbilder för samhällsbyggnad 2020De kommande 15 åren står institutionen för Bygg- och miljöteknik inför stora förändringar. Därför har institutionen initierat projektet Framtidsbilder 2020 där man engagerat en framtidspanel bestående av elva yngre disputerade forskare. Arbetet inleddes med ett breddgruppsmöte där 110 personer representerande institutionens personal och studenter deltog. Vid mötet identifierades ett antal trender och osäkra utvecklingar som påverkar framtiden inom samhällsbyggnadsområdet. Deltagarna bidrog också med idéer till en önskvärd utveckling, vilket har sammanställts och utgör grunden till en gemensam önskvärd framtid/vision för institutionen. Materialet från breddgruppsmötet har bearbetats av Framtidspanelen och resulterat i fyra scenarier som beskriver hur samhällsbyggnadsområdet kan se ut år 2020. Syftet med framtidsbilderna är att de ska vara vägledande för institutionens beslut och förhållningssätt under de kommande åren.Fyra scenarierTurning TorsoSamhället präglas av en ekonomi som är på uppgång, och av ett nytänkande och öppet samhälle. Materiell status och individualism är viktigt. Detta leder till en hög arbetsbelastning samt krav på exklusiva varor av hög kvali-tet. Det finns en stor medvetenhet om miljöpåverkan och klimatförändringar och lösningarna för att klara energiförsörjningen är innovativa.Eco-metropolenDet sveper en grön våg genom dagens samhälle. Under de senaste 15 åren har vi insett att jorden skall vara en bebolig plats även åt dem som kommer efter oss. Vi söker ständigt efter nya, mer förfinade metoder att tillvarata de resurser vi har. Samhället och individen är i balans. Ekonomin är god och vi är miljömedvetna, trygga och integrerade. Nytänkande premieras och icke- materialistiska värderingar står högt i kurs. Vi tänker individuellt, men agerar mer än gärna för kollektivets bästa. Utbildning är gratis TrädgårdsstadenEtt samhälle där vi lärt oss hantera stress, men känner oss otrygga och helst umgås i slutna sociala sammanhang. Vi bor enkelt inne i stan, eller gärna på landsbygden nära storstäderna. Minskade behov av högutbildade i samhället gör att vi har svårt att rekrytera studenter till teknikutbildningar. Det traditionella tankesättet leder till kulturkrockar med företag och personer från andra länder.Gated communitiesFörsämrad ekonomi och ökad egoism har lett fram till ett stressat, otryggt och segregerat samhälle. Accelererande klimatförändringar och ökad miljö-påverkan skrämmer oss, men trots det åtgärdar vi inte problemen, utan koncentrerar oss på konsekvenserna. Arbetslöshet i samhällsbyggnadssek-torn leder till sänkt status för samhällsbyggaren. Vi har därför svårt att rekrytera studenter, och även forskningen har låg status.
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| 4. |
- Andersson, Ulf, 1973-, et al.
(författare)
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Challenges in designing virtual environments training social skills for children with autism
- 2006
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Ingår i: International Journal on Disability and Human Development. - Tel Aviv Israel : Freund Publishing House Ltd. - 1565-012X. ; 5:2, s. 105-111, s. 35-43
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to explore particular challenges faced when designing virtual environments for children with autism, with the purpose of training social skills. Our findings are based on studying autistic behavior during three years (primary and secondary sources), analysis of related system and other computer mediated assistive technology, as well as general game design. From these studies, we have identified eight critical design parameters that must be adjustable in a system suitable for autistic persons. The importance of the parameters, their variation range, as well as the need for independent adjustment of these were estimated and verified by experienced expert pedagogues. Copyright © Freund Publishing House Limited.
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| 5. |
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| 6. |
- Andreasson, Ulf, 1968, et al.
(författare)
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Aspects of beta-amyloid as a biomarker for Alzheimer's disease
- 2007
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Ingår i: Biomarkers in Medicine. - : Future Medicine Ltd. - 1752-0363 .- 1752-0371. ; 1:1, s. 59-78
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Forskningsöversikt (refereegranskat)abstract
- Alzheimer’s disease is an age-related neurodegenerative disorder that results in progressive cognitive impairment and death. The accumulation of β-amyloid (Aβ) in specific brain regions is believed by many to represent the earliest event in the pathogenesis of the disease. Here, we review the key aspects of Aβ as a biomarker for Alzheimer’s disease, including the pathogenicity of Aβ, the possible biological functions of its precursor protein, the Aβ metabolism and homeostasis, the diagnostic performance of different Aβ assays in different settings and the potential usefulness of Aβ as a surrogate marker for treatment efficacy in clinical trials of novel Aβ-targeting drugs against Alzheimer’s disease.
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| 7. |
- Boström, Pontus, 1982, et al.
(författare)
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SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity.
- 2007
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Ingår i: Nature cell biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 9:11, s. 1286-93
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Tidskriftsartikel (refereegranskat)abstract
- The accumulation of cytosolic lipid droplets in muscle and liver cells has been linked to the development of insulin resistance and type 2 diabetes. Such droplets are formed as small structures that increase in size through fusion, a process that is dependent on intact microtubules and the motor protein dynein. Approximately 15% of all droplets are involved in fusion processes at a given time. Here, we show that lipid droplets are associated with proteins involved in fusion processes in the cell: NSF (N-ethylmaleimide-sensitive-factor), alpha-SNAP (soluble NSF attachment protein) and the SNAREs (SNAP receptors), SNAP23 (synaptosomal-associated protein of 23 kDa), syntaxin-5 and VAMP4 (vesicle-associated membrane protein 4). Knockdown of the genes for SNAP23, syntaxin-5 or VAMP4, or microinjection of a dominant-negative mutant of alpha-SNAP, decreases the rate of fusion and the size of the lipid droplets. Thus, the SNARE system seems to have an important role in lipid droplet fusion. We also show that oleic acid treatment decreases the insulin sensitivity of heart muscle cells, and this sensitivity is completely restored by transfection with SNAP23. Thus, SNAP23 might be a link between insulin sensitivity and the inflow of fatty acids to the cell.
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| 8. |
- Franckhauser, S., et al.
(författare)
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Overexpression of Il6 leads to hyperinsulinaemia, liver inflammation and reduced body weight in mice
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:7, s. 1306-16
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: IL-6 is released by the adipose tissue and increased circulating levels in obesity are associated with hyperinsulinaemia and insulin resistance. Short-term experiments suggest that increased IL-6 release by the skeletal muscle following exercise may improve insulin sensitivity. METHODS: In order to examine the effect of chronically elevated IL-6 levels, we overexpressed Il6 in skeletal muscle in mice using an electro-transfer procedure. RESULTS: Circulating IL-6 levels were increased and the animals rapidly lost both weight and body fat, but food intake was unchanged, which is consistent with the finding that IL-6 increased energy expenditure. Insulin levels were inappropriately elevated and combined with hypoglycaemia in spite of reduced 2-deoxy-D: -glucose uptake by skeletal muscle. Insulin-stimulated glucose uptake by skeletal muscles ex vivo was reduced, probably due to the decreased amounts of glucose transporter (GLUT)-4. Beta cell insulin content was increased, while apparent beta cell mass was unchanged. Circulating serum amyloid A cluster levels were increased tenfold due to a pronounced proinflammatory state in the liver with infiltration of inflammatory cells. However, no liver steatosis was found, which may be accounted for by concomitant AMP kinase activation. CONCLUSIONS/INTERPRETATION: Chronically elevated IL-6 levels lead to inappropriate hyperinsulinaemia, reduced body weight, impaired insulin-stimulated glucose uptake by the skeletal muscles and marked inflammation in the liver. Thus, the pleiotrophic effects of chronically elevated IL-6 levels preclude any obvious usefulness in treating obesity or its associated metabolic complications in man, despite the fact that weight reduction may be expected.
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| 9. |
- Gustafson, Birgit, 1951, et al.
(författare)
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Inflamed Adipose Tissue: A Culprit Underlying the Metabolic Syndrome and Atherosclerosis
- 2007
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Ingår i: Arterioscler Thromb Vasc Biol. - 1524-4636. ; 27
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Tidskriftsartikel (refereegranskat)abstract
- The metabolic syndrome is associated with a dysregulated adipose tissue; in part a consequence of adipose cell enlargement and the associated infiltration of macrophages. Adipose cell enlargement leads to a proinflammatory state in the cells with reduced secretion of adiponectin and with increased secretion of several cytokines and chemokines including interleukin (IL)-6, IL-8, and MCP-1. MCP-1 has been shown to play an important role for the associated recruitment of macrophages into the adipose tissue. The increased release of cytokines leads to an impaired differentiation of the preadipocytes with reduced lipid accumulation and induction of adiponectin, thus promoting ectopic lipid storage. In particular tumor necrosis factor (TNF) alpha, but also IL-6, has been shown to induce these effects in preadipocytes and this is associated with an increased Wnt signaling maintaining the cells in an undifferentiated and proinflammatory state. The proinflammatory state in the adipose tissue also leads to a local insulin resistance including an impaired inhibitory effect of insulin on FFA release. The insulin resistance further supports the proinflammatory state because insulin, by itself, is both antilipolytic and antiinflammatory by antagonizing cytokine-induced activation of STAT signaling.
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| 10. |
- Hammarstedt, Ann, 1975, et al.
(författare)
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The effect of PPARgamma ligands on the adipose tissue in insulin resistance
- 2005
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Ingår i: Prostaglandins Leukot Essent Fatty Acids. - : Elsevier BV. - 0952-3278. ; 73:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance is frequently accompanied by obesity and both obesity and type 2 diabetes are associated with a mild chronic inflammation. Elevated levels of various cytokines, such as TNF-alpha and IL-6, are typically found in the adipose tissue in these conditions. It has been suggested that many cytokines produced in the adipose tissue are derived from infiltrated inflammatory cells. However, the adipose tissue itself has proven to be an important endocrine organ, secreting several hormones and cytokines, usually referred to as adipokines. Peroxisome proliferator-activated receptor (PPAR)gamma is essential for adipocyte proliferation and differentiation. In recent years, PPARgamma and its ligands, the thiazolidinediones (TZD), have achieved great attention due to their insulin sensitizing and anti-inflammatory properties. Treatment with TZDs result in improved insulin signaling and adipocyte differentiation, increased adipose tissue influx of free fatty acids and inhibition of cytokine expression and action. As a result, PPARgamma plays a central role in maintaining a functional and differentiated adipose tissue.
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