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- Hoffstedt, J, et al.
(författare)
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Polymorphism in the Calpain 10 gene influences glucose metabolism in human fat cells
- 2002
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 45:2, s. 276-282
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis. A common G to A polymorphism (UCSNP-43) in the Calpain 10 gene was recently found to be associated with Type 11 (non-insulin-dependent) diabetes mellitus and variations in post-absorptive and insulin stimulated glucose metabolism in vivo. We aimed to study the influence of Calpain 10 polymorphism on insulin action in fat cells. Methods. Calpain 10 polymorphism (UCSNP-19, -43 or -63) were set in relation to lipolysis and lipogenesis in isolated subcutaneous adipocytes of 46 apparently healthy non-obese subjects. Results. For UCSNP-43 the GIG genotype had twofold higher basal and insulin stimulated rates as compared with AA/AG genotypes. However, there was no genotype effect on basal or insulin inhibited lipolysis rates in fat cells. The protein amount of GLUT 4 in adipocytes was not influenced by the polymorphism. Fat cells expressed mRNA for the Calpain 10 gene at a relatively high concentration, about 4 amol/mug RNA, which is similar to that of uncoupling protein-2. Neither a UCSNP-19 nor a UCSNP-63 polymorphism in the Calpain 10 gene was found to be associated with basal or insulin-induced adipocyte lipolysis and lipogenesis. None of the polymorphisms influenced body mass index or fasting plasma concentrations of insulin and glucose in 693 non-obese healthy subjects. Conclusion/interpretation. The Calpain 10 gene could be involved in the regulation of glucose metabolism but not lipolysis in human fat cells, although it does not involve adipocyte GLUT-4 protein content. It is possible that the Calpain 10 gene predisposes to diabetes by influencing the glucose metabolism.
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| 7. |
- Lofgren, P, et al.
(författare)
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Major gentler differences in the lipolytic capacity of abdominal subcutaneous fat cells in obesity observed before and after long-term weight reduction
- 2002
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 87:2, s. 764-771
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Tidskriftsartikel (refereegranskat)abstract
- The influence of obesity on the lipolytic capacity of isolated se fat cells was studied prospectively in 13 women and 10 men, all obese, but otherwise healthy, before and 2 and 3 yr after weight reduction by bariatric surgery. Nonobese subjects (25 women and 17 men) without a family history of obesity served as the control group. Lipolytic capacity was determined after stimulation at different steps of the lipolytic cascade with noradrenaline, isoprenaline, forskolin, and (Bu)(2)AMP. Bariatric surgery was followed by a marked and similar reduction of body mass index and fat cell volume (similar to40%) in both genders. Before weight loss, lipolytic capacity per cell was elevated in obese women and decreased to normal levels after weight reduction at 2 and 3 yr. However, lipolytic capacity per fat cell surface area was not changed in obese women. In obese men, lipolytic capacity per cell was almost the same as in lean men and was not influenced by weight reduction. Lipolytic capacity was related to fat cell size in women (P=0.0008; r=0.58), but not in men (P=0.67; r=0.086). The protein content of hormone-sensitive lipase, which determines lipolytic capacity, was significantly lower in obese men and women and increased slightly after weight reduction in men only. Thus, in women, but not in men, the adipocyte lipolytic capacity is influenced by obesity and weight reduction, probably due to changes in fat cell size. These gender differences are not related to the amount of hormone-sensitive lipase protein in adipocytes.
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- Lofgren, P, et al.
(författare)
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Secretion of tumor necrosis factor-alpha shows a strong relationship to insulin-stimulated glucose transport in human adipose tissue
- 2000
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 49:5, s. 688-692
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Tidskriftsartikel (refereegranskat)abstract
- Some animal models suggest that tumor necrosis factor (TNF)-alpha is a key component in obesity-linked insulin resistance because it inhibits insulin receptor signaling and glucose transport in insulin-sensitive tissues. However, in vivo data in humans have given conflicting results regarding the relationship between circulating TNF-alpha levels and insulin sensitivity. In the present study, the potential local role of TNF-alpha on insulin action in human subcutaneous adipose tissue was studied in 42 obese women (BMI 39+/-10 kg/m2). We found a strong inverse correlation between adipose TNF-alpha secretion and maximum insulin-stimulated glucose transport in adipocytes that was independent of fat cell volume, age, and BMI (P < 0.001, r = 0.58). As much as one-third of the variation in insulin-stimulated glucose transport could be accounted for by variations in TNF-alpha secretion. There was no significant correlation (r = 0.11) between secretion of adipose plasminogen activator inhibitor 1 and glucose transport. Furthermore, subcutaneous adipose tissue of 4 obese women (BMI 40+/-4) incubated with TNF-A for 24 h showed a one-third concentration-dependent inhibition of insulin-stimulated glucose transport (P < 0.01). In conclusion, adipose TNF-alpha may be an important specific and local factor in adipose tissue that influences the ability of insulin to stimulate glucose transport in human fat cells, at least in obese women.
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- Al-Khalili, F, et al.
(författare)
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Clinical importance of risk factors and exercise testing for prediction of significant coronary artery stenosis in women recovering from unstable coronary artery disease : The Stockholm Female Coronary Risk Study
- 2000
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Ingår i: American Heart Journal. - Karolinska Hosp & Inst, Dept Cardiol, Stockholm, Sweden. Karolinska Hosp & Inst, Dept Thorac Radiol, Stockholm, Sweden. Karolinska Hosp & Inst, Dept Publ Hlth Sci, Div Prevent Med, Stockholm, Sweden. : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 139:6, s. 971-978
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Tidskriftsartikel (refereegranskat)abstract
- Background The objectives of this study were to investigate the relation between coronary risk factors, exercise testing parameters, and the presence of angiographically significant coronary artery disease (CAD) (>50% luminal stenosis) in female patients previously hospitalized for an acute CAD event. Methods and Results All women younger than age 66 years in the greater Stockholm area in Sweden who were hospitalized for acute coronary syndromes during a 3-year period were recruited, Besides collection of clinical parameters, coronary angiography and a symptom-limited exercise test were performed in 228 patients 3 to 6 months after the index hospitalization. The mean age was 56 +/- 7 years. Angiographically nonsignificant CAD (stenosis <50%) was verified in 37% of the patients; significant CAD was found in 63%. The clinical parameters that showed the strongest relation with the presence of significant CAD after adjusting for age were history of myocardial infarction (odds ratio [OR] 4.91, 95% confidence interval [CI] 2.35 to 7.49), history of diabetes mellitus (OR 3.83, 95% Cl 1.63 to 14.31), serum high-density lipoprotein cholesterol <1.4 mmol/L (OR 2.11, 95% Cl 1.20 to 3.72), and waist-to-hip ratio >0.85 (OR 1.78, 95% Cl 1.02 to 3.10). A low exercise capacity and associated low change of rate-pressure product from rest to peak exercise were the only exercise testing parameters that were significantly related to angiographically verified significant CAD (<90% of the predicted maximal work capacity adjusted for age and weight, OR 1.91, 95% CI 1.04 to 3.50). Conclusions In female patients recovering from unstable CAD, exercise capacity was the only exercise testing parameter of value in the prediction of significant CAD. The consideration of certain clinical characteristics and coronary risk factors offer better or complementary information when deciding on further coronary assessment.
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| 13. |
- Al-Khalili, F, et al.
(författare)
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Clinical predictors of poor outcome in women recovering from acute coronary syndrome
- 2000
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Ingår i: Journal of the American College of Cardiology. - Karolinska Hosp, Dept Cardiol, S-10401 Stockholm, Sweden. Karolinska Hosp, Dept Publ Hlth Sci, Div Prevent Med, S-10401 Stockholm, Sweden. Karolinska Hosp, Dept Thorac Radiol, S-10401 Stockholm, Sweden. Karolinska Inst, Stockholm, Sweden. : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 35:2, s. 392A-392A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Ek, I, et al.
(författare)
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A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance
- 2002
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 51:2, s. 484-492
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Tidskriftsartikel (refereegranskat)abstract
- The etiology of polycystic ovary syndrome (PCOS) is unknown. However, PCOS has a strong resemblance to the insulin resistance (metabolic) syndrome, where an increased rate of visceral fat cell lipolysis is believed to play a pathophysiological role. We hypothesized that primary defects in visceral lipolysis might also exist in PCOS. Ten young, nonobese, and otherwise healthy PCOS women were compared with 13 matched control women. In vitro lipolysis regulation and stoichiometric properties of the final step in lipolysis activation, namely the protein kinase A (PKA)-hormone sensitive lipase (HSL) complex, were investigated in isolated visceral (i.e., omental) fat cells. Body fat distribution and circulating levels of insulin, glucose, and lipids were normal in PCOS women. However, in vivo insulin sensitivity was slightly decreased (P = 0.03). Catecholamine-induced adipocyte lipolysis was markedly (i.e., about twofold) increased in PCOS women due to changes at the postreceptor level, although there was no change in the antilipolytic properties of visceral fat cells. Western blot analyses of visceral adipose tissue showed twofold increased levels of the catalytic and the regulatory la components of PKA. In contrast, the regulatory RIIbeta component of PKA was almost 50% decreased in visceral adipose tissue in PCOS women. Recent studies on genetically modified mice have shown that a similar transition in the regulatory PKA units induces an increased lipolytic response to catecholamines. Further analysis showed that the level of HSL-short, an enzymatically inactive splice form of HSL, was decreased in PCOS (P < 0.01). The altered lipolysis in PCOS is different from that observed in visceral fat cells in the insulin resistance syndrome that occurs at the level of adrenergic receptors. We concluded that increased catecholamine-induced lipolysis in visceral fat cells may be due to unique alterations in the stoichiometric properties of the adipose PKA-HSL holoenzymes. This could be an early and possibly primary lipolysis defect in PCOS.
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- Hagstrom-Toft, E, et al.
(författare)
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Marked heterogeneity of human skeletal muscle lipolysis at rest
- 2002
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:12, s. 3376-3383
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Tidskriftsartikel (refereegranskat)abstract
- In this study, variations in lipolysis among different muscle groups were examined by measuring local net glycerol release in vivo in healthy, normal-weight subjects (n = 11) during rested, postabsorptive conditions. Microdialysis of the gastrocnemius, deltoid, and vastus lateralis muscle regions revealed that extracellular glycerol concentrations of these three muscle regions were 84.7 ± 6.7, 59.7 + 7.3, and 56.4 ± 7.5 μmol/l, respectively, and the arterial plasma glycerol concentration was 44.8 ± 2.3 μmol/l (P = 0.0003–0.006, gastrocnemius vs. others). Local tissue blood flow, as measured by Xe clearance, did not differ among the regions. Net glycerol release was significantly higher in gastrocnemius muscle than in the two other regions. There were no regional differences in glycerol uptake when studied during glycerol infusion. Gastrocnemius muscle showed a dominance of type 1 fibers (70%), whereas the vastus lateralis muscle had equal distribution of fiber types (P = 0.02). No differences in intramuscular triaclyceride content, perimuscular fat, or the adipocyte-specific protein perilipin were observed among the muscle regions. Triglyceride turnover in the gastrocnemius muscle was 3.3 + 1.4% over 24 h, which is about 10 times more rapid than the turnover rate in subcutaneous adipose tissue (P < 0.01). Thus there were marked differences in lipolytic activity among skeletal muscle groups at rest, possibly reflecting variations in fiber type.
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| 25. |
- Kjölhede, Preben, 1957-, et al.
(författare)
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Abdominal urethrocystopexy using fibrin sealant. A prospective study of long-term efficacy
- 2000
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Ingår i: International Urogynecology Journal. - : Springer Science and Business Media LLC. - 0937-3462 .- 1433-3023. ; 11:2, s. 93-96
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Tidskriftsartikel (refereegranskat)abstract
- Over the past decade efforts have been made to develop less invasive surgical treatment for female stress urinary incontinence (SUI). Abdominal urethrocystopexy with fibrin sealant combined with a couple of absorbable sutures has previously been reported as a promising method. This prospective observational study was aimed at evaluating the efficacy and safety of abdominal urethrocystopexy through a minilaparotomy using solely fibrin sealant (Tisseel) as the fixation glue. Forty-three women with objectively proven SUI were operated upon with this method. The subjective cure rates at 1 and 3 years' follow-up were 72% and 55%, respectively. The corresponding objective cure rates were 64% and 60%. No serious major operative complications occurred. One patient had transient urinary retention for 3 months. Otherwise, micturition was established within a median 1 day (range 1-3 days) after the operation. The result of this pilot study indicates a cure rate lower than that obtained with the conventional abdominal Burch colposuspension. Thus the method cannot be recommended as a standard procedure for treatment of SUI.
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- Ryden, L, et al.
(författare)
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European role in global cardiology
- 2000
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Ingår i: Lancet (London, England). - 0140-6736. ; 355:9198, s. 149-150
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 32. |
- Ryden, M, et al.
(författare)
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Effect of the (C825T) Gbeta(3) polymorphism on adrenoceptor-mediated lipolysis in human fat cells
- 2002
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:5, s. 1601-1608
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Tidskriftsartikel (refereegranskat)abstract
- A common Gβ3 gene polymorphism (C825T) influences G protein receptor-mediated signal transduction. We investigated whether this polymorphism influences lipolysis in isolated subcutaneous fat cells from 114 healthy obese subjects. The Gβ3 protein content was markedly decreased in adipocytes of TT carriers, but the alternatively spliced short form of Gβ3 previously shown in platelets of 825T carriers was not detected. Fat cells of TT carriers showed a significant 10-fold decrease in the half-maximum effective concentration of agonists selective for lipolytic β1- and β2-adrenoceptors as well as for the antilipolytic α2A-adrenoceptor. In TT carriers, maximum β-adrenoceptor agonist-stimulated lipolysis was decreased, but the maximum antilipolytic effect of α2-adrenoceptors was less marked. Norepinephrine induced adipocyte lipolysis and circulating fasting levels of free fatty acids and glycerol were reduced by half in TT carriers. The polymorphism did not influence the adipocyte content of α2A-adrenoceptors, β2-adrenoceptors, Gαi, or Gαs. In conclusion, the C825T variant of Gβ3 influences lipolysis. Adipocytes of TT carriers have a lower Gβ3 protein content and a decreased function of native Gs- as well as Gi-coupled adrenoceptors, which reduces the lipolytic effect of catecholamines. These data differ from those obtained in other cell systems that have shown increased expression of an alternative spliced Gβ3 variant and enhanced G protein signaling in 825T carriers, indicating that the polymorphism has cell type-specific effects that may be of importance for type 2 diabetes and other insulin-resistant conditions.
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| 37. |
- van Harmelen, V, et al.
(författare)
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Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes
- 2002
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:7, s. 2029-2036
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Tidskriftsartikel (refereegranskat)abstract
- Site differences in adipose tissue function may have implications for insulin-resistant conditions. In mature adipose tissue, subcutaneous adipocytes have higher leptin secretion, similar tumor necrosis factor (TNF)-α secretion, and lower catecholamine-stimulated lipolysis as compared with omental adipocytes. In this study, lipolysis and leptin and TNF-α secretion were compared between human omental and subcutaneous preadipocytes. After 16 days of incubation in a minimal differentiation medium, leptin mRNA and secretion were found to be two to eight times higher in subcutaneous than omental preadipocytes (P < 0.05). On the other hand, norepinephrine-induced lipolysis was about two times higher in the omental than in the subcutaneous preadipocytes, whereas basal lipolysis did not differ between the two regions. TNF-α secretion was marginally but significantly higher in the omental than in the subcutaneous preadipocytes. Preadipocyte differentiation was equal in both regions and was augmented to the same extent by different thiazolidinediones (rosiglitazone, pioglitazone, or troglitazone) in the two depots. In the presence of rosiglitazone, leptin secretion remained about three times higher and norepinephrine-induced lipolysis about six times lower in subcutaneous as compared with omental preadipocytes (P < 0.05), whereas TNF-α secretion and basal lipolysis were similar in preadipocytes from the two regions. These findings remained unaltered even if rosiglitazone was removed from the medium. However, leptin mRNA showed no regional differences in rosiglitazone-treated cells. Thus, regional differences in adipocyte leptin secretion as well as in norepinephrine-induced lipolysis are marked and present during different stages of preadipocyte differentiation and seem to be determined by intrinsic (i.e., primary) factors.
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| 38. |
- Wanby, Pär, et al.
(författare)
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The FABP2 gene polymorphism in cerebrovascular disease
- 2004
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Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 110:6, s. 355-360
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Tidskriftsartikel (refereegranskat)abstract
- Objective – Earlier studies have shown that the fatty acid binding protein 2 (FABP2) T54 allele is associated with dyslipidemia, which in turn correlates with the incidence of cerebrovascular disease (CVD). To assess whether the FABP2 gene A54T polymorphism is associated with an increased risk of CVD we undertook a case–control study.Materials and methods – A total of 407 patients diagnosed with acute CVD and 158 control subjects were genotyped for the A54T polymorphism using a PCR-RFLP method.Results – Allele and genotype frequencies of the FABP2 A54T polymorphism did not differ between subjects with acute CVD (TT, 9.6%; TA, 41.0%; AA, 49.4%) and controls (TT, 7.6%; TA, 41.1%; AA, 51.3%; P = ns) or in the following subgroups of CVD compared with controls: non-cardioembolic infarction (n = 252), intracerebral hemorrhage (n = 23), and cardioembolic infarction (n = 91). In transient ischemic attacks (TIAs) (n = 41) the combined TT and TA genotype frequency (TT + TA, 65.9%) was more frequent than in controls (48.7%) (P = 0.05). Furthermore, the TT genotype was more frequent in non-smoking patients under the age of 70 (n = 77) with a non-cardioembolic infarction (TT, 18.2%) compared with controls (7.6%) (P = 0.024).Conclusions – Our findings suggest an involvement of the FABP2 (A54T) gene polymorphism in the pathogenesis of CVD. The FABP2 T54 allele appears to be a genetic susceptibility marker for TIA and non-cardioembolic infarction at younger onset.
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