| 1. |
|
|
| 2. |
- Burén, Jonas, 1972-
(författare)
-
Glucose and lipid metabolism in insulin resistance : an experimental study in fat cells
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 diabetes is usually caused by a combination of pancreatic β-cell failure and insulin resistance in target tissues like liver, muscle and fat. Insulin resistance is characterised by an impaired effect of insulin to reduce hepatic glucose production and to promote glucose uptake in peripheral tissues. The focus of this study was to further elucidate cellular mechanisms for insulin resistance that may be of relevance for type 2 diabetes in humans. We used rat and human adipocytes as an established model of insulin’s target cells. Glucocorticoids, e.g. cortisol, can induce insulin resistance in vivo. In the present study, pretreatment of rat adipocytes in vitro for 24 h with the cortisol analogue dexamethasone produced a downregulation of glucose uptake capacity as well as a marked depletion of cellular insulin receptor substrate 1 (IRS-1) and protein kinase B (PKB), two proteins suggested to play a critical role in the intracellular signal transduction pathway of insulin. The amount of phosphorylated PKB in response to acute insulin treatment was decreased in parallel to total PKB content. The basal rate of lipolysis was enhanced, but insulin’s antilipolytic effect was not consistently altered following dexamethasone pretreatment. Alterations in blood glucose as well as insulin levels may be of great importance for cellular as well as whole-body insulin resistance. High glucose (≥15 mM) for 24 h induced a decrease in glucose uptake capacity in rat adipocytes and IRS-1 content was reduced whereas IRS-2 was increased. Long-term pretreatment with a high insulin concentration downregulated insulin binding capacity and when combined with high glucose, it produced a pronounced reduction of cellular IRS-1 and 2 content together with insensitivity to insulin’s effect to activate PKB and a decrease in glucose uptake capacity. A common denominator for a decrease in glucose uptake capacity in our rat adipocyte studies seems to be a decrease in IRS-1 content. Adipocytes from type 2 diabetes patients are insulin-resistant, but in our work the insulin resistance could be reversed by incubation of the cells at a physiological glucose level for 24 h. Insulin resistance in fresh adipocytes from type 2 diabetes patients was associated with in vivo insulin resistance and glycemic level and with adipocyte cell size and waist-hip ratio (WHR). As a potential mechanism for postprandial dyslipidemia in type 2 diabetes, we examined the nutritional regulation of subcutaneous adipose tissue lipoprotein lipase (LPL) activity. It was upregulated by ~40-50 % after a standardised lipid-enriched meal and this was very similar in type 2 diabetes patients and control subjects, suggesting that the postprandial hypertriglyceridemia found in type 2 diabetes is not explained by an altered nutritional regulation of LPL in subcutaneous fat. In conclusion, the present work provides evidence for novel interactions between glucocorticoids and insulin in the regulation of glucose metabolism that may potentially contribute to the development of insulin resistance. High levels of glucose and insulin produce perturbations in the insulin signalling pathway that may be of relevance for human type 2 diabetes. Cellular insulin resistance may be secondary to the diabetic state in vivo, e.g. via glucotoxicity. This is supported by our finding that insulin resistance in adipocytes from type 2 diabetes patients can be reversed after incubation at a physiological glucose level. Key words: adipocyte, insulin resistance, type 2 diabetes, insulin signalling, glucose uptake, insulin, glucose, dexamethasone, insulin receptor substrate, protein kinase B, GLUT4, lipoprotein lipase.
|
|
| 3. |
- Alenius, Gerd-Marie, 1957-
(författare)
-
A Clinical and Genetic Study of Psoriatic Arthritis
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. PsA has a heterogeneous pattern, expressed by different manifestations such as mild mono-oligoarthritis or very severe, erosive and destructive polyarthritis. Measurable inflammatory activity is not always prominent. The aetiology is unknown but genetic factors are believed to be of importance. The pattern of inheritance is proposed to be polygenic. The aim of this study was to estimate the prevalence of joint and axial manifestations, characterise the disease in relation to inflammatory and genetic markers, and to identify disease susceptibility gene(s) for PsA in patients from northern Sweden. All patients from the city of Umeå (n=276), selected from a community and hospital based psoriasis register (n=1737) at the Dept of Dermatology, were invited to a prevalence study. Two hundred-two patients were examined and 97 (48%) had inflammatory manifestations such as peripheral arthritis, axial disease, undifferentiated spondylarthropathy (uSpA) and enthesopathies. Of the 67 patients (33 %) with peripheral arthritis and/or axial disease, 30 were not previously diagnosed. The association of clinical manifestations and potential markers of aggressive joint disease with HLA associations were analysed in 88 patients with PsA. We were not able to confirm findings of other groups reporting strong association with several HLA-antigens. The prevalence of HLA-B17, B37 and B62 was increased compared with controls, but the strongest predictive factors among our patients for an aggressive disease, in a multiple logistic analysis, were polyarthritic disease and distal interphalangeal engagement. In order to investigate for disease susceptibility genes, five genetic loci were analysed with microsatellites and single nucleotide polymorphisms in an association study of 120 patients with PsA. There was a significant association with the TNFB locus on chromosome 6p but not with any other loci examined; 1q21 (PSORS4), 3q21 (PSORS5), 8q24 and CTLA4. When stratifying for the TNFB alleles the association was confined to allele 123. In a subgroup of patients who were HLA-typed (n=83), we were not able to verify linkage disequilibrium with the TNFB allele 123 and the HLA antigens; B17, B27, B37, B62 or Cw*0602. The presence of renal abnormalities was evaluated as a manifestation of systemic inflammation in 73 patients with PsA. Renal abnormalities defined as decreased creatinine-clearance (≤ mean - 2SD) and/or urinary albumin >25 mg/24 h was found in 23% of the patients. The predictive factors for renal abnormalities was inflammatory activity (ESR > 25 mm/h and/or CRP >15 mg/L) indicating a systemic effect in some of the patients. In conclusion, we found high prevalence of inflammatory manifestations in patients with psoriasis. There was no strong association between PsA and HLA antigens and predictive factors for aggressive disease were polyarthritic disease and DIP joint engagement. The TNFB locus was associated with PsA and there were no linkage disequilibrium with the HLA antigens B17, B27, B62 or Cw*0602. There were evidence for systemic effects as renal abnormalities in patients with PsA and measurable inflammatory activity.
|
|
| 4. |
- Alfredsson, Lars, et al.
(författare)
-
Job strain and major risk factors for coronary heart disease. : Baseline results from the WOLF Study
- 2002
-
Ingår i: Scandinavian Journal of Work, Environment & Health. - 0355-3140. ; 28:4, s. 238-248
-
Tidskriftsartikel (refereegranskat)abstract
- The results do not support the hypothesis that job strain has an adverse impact on serum total cholesterol and plasma fibrinogen levels. They suggest that an increased risk of coronary heart disease in association with job strain, if causal, is mediated by other factors, possibly partly by hypertension and low levels of high-density lipoprotein cholesterol.
|
|
| 5. |
|
|
| 6. |
- Brattberg, Gunilla
(författare)
-
Do pain problems in young school children persist into early adulthood? : A 13-year follow-up
- 2004
-
Ingår i: European Journal of Pain. - : Elsevier. - 1090-3801 .- 1532-2149. ; 8:3, s. 187-199
-
Tidskriftsartikel (refereegranskat)abstract
- Design. In a longitudinal study, 335 children ages 8, 11 and 14, first studied in 1989 were followed-up on two occasions in 1991 and 2002. The subjects filled in questionnaires on pain, the first two times in school, the last as a postal survey. Purposes. To determine if headache and back pain during the school years were transitory or if they grew into pain problems in adulthood; to determine predictors of pain. Results. In the 2002 study, 59% of the women and 39% of the men reported pain at 21, 24 and 27 years. A total of 68 (52 women, 16 men) or 20% of the subjects reported pain symptoms in all three studies. The cumulative incidence rate for the presence of pain in the cohort studied was 31% for 1989–2002 and 43% for 1991–2002. Four of the 10 individuals with pain also reported signs of stress. Three predictors were found: reported back pain in 8–14-year-olds (p<0.0001); reported headaches once a week or more in the same age group (p<0.0001); and a positive response in the ages 10–16 to the question: “Do you often feel nervous?” (OR=2.1, 95% CI 1.3–3.4). When adjusted for age, sex and all psychosocial risk determinants studied in multiple logistic regression, a positive answer to this question was a significant predictor of pain in young adulthood. A positive response by the 10–16-year-olds to “Do you find it difficult to describe your feelings?” was a predictor of pathological anxiety in early adulthood, but stress perceived in childhood/adolescence did not predict future pain or stress. Conclusions. Since pain reports in childhood and early adolescence seem to be associated with the report of pain in early adulthood, more attention should be given to the way ill-health is managed in adolescence in this vulnerable group.
|
|
| 7. |
|
|
| 8. |
- Brostedt, Erika M., et al.
(författare)
-
Job strain och PAI-1
- 2002
-
Ingår i: Psykosocial belastning och riskfaktorer för hjärt-kärlsjukdom : Minisymposium i WOLF-projektet 8 februari 2001. - Stockholm : Arbetslivsinstitutet. - 9170456410 ; , s. 3-6
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 9. |
|
|
| 10. |
- Bylund, Sonya H, 1953-
(författare)
-
Hand-arm vibration and working women : Consequences and affecting factors
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The use of hand-held vibrating tools may lead to hand-arm vibration syndrome (HAVS), a condition with vascular, neurological and musculoskeletal symptoms. Vibrating tools are used in several occupations in which women can be found, e.g. by metal- and wood workers, drivers, and dental personnel. The risk of women developing HAVS is hard to estimate, as little research has been done on women exposed to hand-arm vibration. The overall aim of this thesis has been to fill this gap of knowledge. It is based upon one questionnaire study and one interview study on women who have reported an occupational injury related to hand-arm vibration. The thesis also comprises two laboratory studies of female and male subjects exposed to hand-arm vibration from a handle. The questionnaire and the interview study showed that the women had a high prevalence of symptoms, such as numbness, weakness, pain and white fingers. Neurological symptoms were more common and developed after shorter time of exposure compared to vascular symptoms. The symptoms had a considerable impact on all domains of the women’s lives, not only on their physical functioning, such as the ability to work, to participate in leisure activities and to do household activities, but also on their relationships and identity. Forty per cent of the women had retired or retrained due to the injury. Dental personnel had the highest relative risk of vibration injuries. In one of the laboratory studies 12 female and 12 male subjects were exposed to vibration in two vibration directions, (Xh and Zh) and at two vibration levels. The absorbed power was higher in the Zh direction and at the higher vibration level. The volumes of the subjects’ arms affected the power absorption in the Zh direction. There were no indications of a gender difference in the absorption of power. In the other laboratory study, the effect of handle size, vibration level, anthropometric measures and maximal grip force on the ability to perform a precision task was studied in 20 female and 20 male subjects. Ratings of difficulty and discomfort were made after each test round. The results indicate that the male subjects performed better in all the tests, but no gender difference was seen in the ratings. The higher vibration level resulted in higher ratings of discomfort. In the female subjects, the handle size, the anthropometric measures and maximal grip force affected both the performance and the ratings. In conclusion, the studies indicate that vibration injuries are severely disabling and influence many parts of the sufferer’s life. Vibration injuries are preventable, and the extensive consequences found underscore the importance of preventive action. This can be done by informing employees about the risks, and by giving them the opportunity to choose suitable machines and to practice work tasks when starting a new job.
|
|
