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- Hammarstedt, Ann, 1975, et al.
(author)
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Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects
- 2005
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 48:1, s. 96-104
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Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: We examined whether short-term treatment with a thiazolidinedione improves insulin sensitivity in non-obese but insulin-resistant subjects and whether this is associated with an improvement in dysregulated adipose tissue (reduced expression of IRS-1, GLUT4, PPARgamma co-activator 1 and markers of terminal differentiation) that we have previously documented to be associated with insulin resistance. METHODS: Ten non-diabetic subjects, identified as having low IRS-1 and GLUT-4 protein in adipose cells as markers of insulin resistance, underwent 3 weeks of treatment with pioglitazone. The euglycaemic-hyperinsulinaemic clamp technique was used to measure insulin sensitivity before and after treatment. Serum samples were analysed for glucose, insulin, lipids, total and high-molecular-weight (HMW) adiponectin levels. Biopsies from abdominal subcutaneous adipose tissue were taken, cell size measured, mRNA and protein extracted and quantified using real-time RT-PCR and Western blot. RESULTS: Insulin sensitivity was improved after 3 weeks treatment and circulating total as well as HMW adiponectin increased in all subjects, while no effect was seen on serum lipids. In the adipose cells, gene and protein expression of IRS-1 and PPARgamma co-activator 1 remained unchanged, while adiponectin, adipocyte P 2, uncoupling protein 2, GLUT4 and liver X receptor-alpha increased. Insulin-stimulated tyrosine phosphorylation and p-ser-PKB/Akt increased, while no significant effect of thiazolidinedione treatment was seen on the inflammatory status of the adipose tissue in these non-obese subjects. CONCLUSIONS/INTERPRETATION: Short-term treatment with pioglitazone improved insulin sensitivity in the absence of any changes in circulating NEFA or lipid levels. Several markers of adipose cell differentiation, previously shown to be reduced in insulin resistance, were augmented, supporting the concept that insulin resistance in these individuals is associated with impaired terminal differentiation of the adipose cells.
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| 2. |
- Hammarstedt, Ann, 1975, et al.
(author)
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Visfatin is an adipokine, but it is not regulated by thiazolidinediones
- 2006
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In: J Clin Endocrinol Metab. - : The Endocrine Society. - 0021-972X. ; 91:3, s. 1181-4
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Journal article (peer-reviewed)abstract
- CONTEXT: Visfatin was recently reported to be expressed in human adipose tissue and to exert insulin-mimicking effects. OBJECTIVE: The objective of this study was to examine whether visfatin is a true adipokine and is expressed in isolated fat cells. We also examined whether visfatin is regulated by thiazolidinediones and, thus, can contribute to the ability of these agents to improve insulin sensitivity. DESIGN: This was an open-labeled drug therapy trial. SETTING: This study was performed at a university hospital. PATIENTS: Seven newly diagnosed and previously untreated type 2 diabetic patients and six healthy individuals with reduced insulin sensitivity participated in the study. INTERVENTION: Pioglitazone therapy (30-45 mg/d) was given for 3-4 wk. MAIN OUTCOME MEASURES: Serum and adipose tissue mRNA levels of visfatin and adiponectin were the main outcome measures. RESULTS: Visfatin mRNA is expressed in both adipose tissue and isolated adipocytes. Treatment with thiazolidinediones for 3-4 wk did not alter the gene expression or circulating levels of visfatin in either nondiabetic or the diabetic individuals, whereas adiponectin increased significantly. CONCLUSION: The present study shows that visfatin is a true adipokine, but it is not regulated by TZD and, thus, is unlikely to contribute to the insulin-sensitizing actions of these drugs.
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| 3. |
- Rotter Sopasakis, Victoria, 1972, et al.
(author)
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High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator
- 2004
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In: Obes Res. - 1071-7323. ; 12:3, s. 454-60
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine the possibility that interleukin-6 (IL-6) can act as a paracrine regulator in adipose tissue by examining effects on adipogenic genes and measuring interstitial IL-6 concentrations in situ. RESEARCH METHODS AND PROCEDURES: Circulating and interstitial IL-6 concentrations in abdominal and femoral adipose tissue were measured using the calibrated microdialysis technique in 20 healthy male subjects. The effects of adipose cell enlargement on gene expression and IL-6 secretion were examined, as well as the effect of IL-6 in vitro on gene expression of adiponectin and other markers of adipocyte differentiation. RESULTS: The IL-6 concentration in the interstitial fluid was approximately 100-fold higher than that in plasma, suggesting that IL-6 may be a paracrine regulator of adipose tissue. This was further supported by the finding that adding IL-6 in vitro at similar concentrations down-regulated the expression of adiponectin, aP2, and PPARgamma-2 in cultured human adipose tissue. In addition, gene expression and release of IL-6, both in vivo and in vitro, correlated with adipose cell size. DISCUSSION: These data suggest that IL-6 may be a paracrine regulator of adipose tissue. Furthermore, increased adipose tissue production of IL-6 after hypertrophic enlargement of the adipose cells may detrimentally affect systemic insulin action by inducing adipose tissue dysfunction with impaired differentiation of the pre-adipocytes and/or adipocytes and lower adiponectin.
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