| 1. |
- Borg, Jörgen, et al.
(författare)
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Perilipin is present in islets of Langerhans and protects against lipotoxicity when overexpressed in the beta-cell line INS-1.
- 2009
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 150:7, s. 3049-3057
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Tidskriftsartikel (refereegranskat)abstract
- Lipids have been shown to play a dual role in pancreatic beta-cells - a lipid-derived signal appears to be necessary for glucose-stimulated insulin secretion, whereas lipid accumulation causes impaired insulin secretion and apoptosis. The ability of the protein perilipin to regulate lipolysis prompted an investigation of the presence of perilipin in the islets of Langerhans. In this study evidence is presented for perilipin expression in rat, mouse and human islets of Langerhans as well as in the rat clonal beta-cell line INS-1. In rat and mouse islets, perilipin was verified to be present in beta-cells. In order to examine if the development of lipotoxicity could be prevented by manipulating the conditions for lipid storage in the beta-cell, INS-1 cells with adenoviral-mediated overexpression of perilipin were exposed to lipotoxic conditions for 72 hours. In cells exposed to palmitate, perilipin overexpression caused increased accumulation of triacylglycerols and decreased lipolysis compared to control cells. Whereas glucose-stimulated insulin secretion was retained following palmitate exposure in cells overexpressing perilipin, it was completely abolished in control beta-cells. Thus, overexpression of perilipin appears to confer protection against the development of beta-cell dysfunction following prolonged exposure to palmitate by promoting lipid storage and limiting lipolysis.
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| 2. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 3. |
- Ling, Charlotte, et al.
(författare)
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Calpain-10 expression is elevated in pancreatic islets from patients with type 2 diabetes.
- 2009
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Calpain-10 was the first gene to be identified influencing the risk of type 2 diabetes (T2D) by positioning cloning. Studies in beta-cell lines and rodent islets suggest that calpain-10 may act as a regulator of insulin secretion. However, its role in human pancreatic islets remains unclear. The aim of this study was to examine if calpain-10 expression is altered in islets from patients with T2D and if the transcript level correlates with insulin release. We also tested if polymorphisms in the CAPN10 gene are associated with gene expression and insulin secretion in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Calpain-10 mRNA expression was analysed in human pancreatic islets from 34 non-diabetic and 10 T2D multi-organ donors. CAPN10 SNP-43 and SNP-44 were genotyped and related to gene expression and insulin release in response to glucose, arginine and glibenclamide. The mRNA level of calpain-10 was elevated by 64% in pancreatic islets from patients with T2D compared with non-diabetic donors (P = 0.01). Moreover, the calpain-10 expression correlated positively with arginine-stimulated insulin release in islets from non-diabetic donors (r = 0.45, P = 0.015). However, this correlation was lost in islets from patients with T2D (r = 0.09; P = 0.8). The G/G variant of SNP-43 was associated with reduced insulin release in response to glucose (P
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| 4. |
- Lupi, Angelo, et al.
(författare)
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Multi-seasonal ultrafine aerosol particle number concentration measurements at the Gruvebadet observatory, Ny-lesund, Svalbard Islands
- 2016
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Ingår i: Rendiconti lincei scienze fisiche e naturali. - : Springer Science and Business Media LLC. - 2037-4631. ; 27, s. 59-71
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Tidskriftsartikel (refereegranskat)abstract
- The object of this study was to investigate the different modal behavior of ultrafine aerosol particles collected at the Gruvebadet observatory located in Ny-lesund (Svalbard Islands, 78A degrees 55'N, 11A degrees 56'E). Aerosol particle size distribution was measured in the size range from 10 to 470 nm typically from the beginning of spring to the beginning of fall during four (non-consecutive) years (2010, 2011, 2013 and 2014). The median concentration for the whole period taken into account was 214 particles cm(-3), oscillating between the median maximum in July with a concentration of 257 particles cm(-3) and a median minimum in April with 197 particles cm(-3). The median total number concentration did not present a well-defined seasonal behavior, as shown by contrast looking at the sub/modal number concentration, where distinct trends appeared in the predominant accumulation concentration recorded during April/May and the preponderant concentration of Aitken particles during the summer months. Lastly, the short side-by-side spring 2013 campaign performed at the Zeppelin observatory with a differential mobility particle sizer was characterized by an aerosol concentration mean steady difference between the two instruments of around 14 %, thereby supporting the reliability of the device located at Gruvebadet.
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| 5. |
- Lupi, Claudia, et al.
(författare)
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Do sample preparation techniques affect the relative abundance of Florisphaera profunda?
- 2016
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Ingår i: Marine Micropaleontology. - : Elsevier BV. - 0377-8398 .- 1872-6186. ; 127, s. 42-49
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Tidskriftsartikel (refereegranskat)abstract
- We investigated which method among smearing, settling, filtration, and random settling is the most accurate for determining the relative abundance of Florisphaera profunda. This species is included in paleoproductivity indices because it is one of the most important deep-water dwellers. Therefore, an accurate assessment of its relative abundance is key to monitoring variations in thermocline and nutricline depths. The low birefringence and flat polygonal shape of F. profunda may lead to inaccurate estimates of its relative abundance as it is poorly visible under light microscopy (LM), and different sample preparation may affect the number of specimens on each slide. We studied eight samples from the Ocean Drilling Program (ODP) Site 1209B (Shatslcy Rise, NW Pacific) from the last 450 kyr. Each sample was prepared five times using each technique for a total of 160 slides. Through a rigorous analytical and statistical approach, we demonstrated the high reproducibility of each method and showed good agreement among techniques at low percentages of F. profunda. When the percentage of this species increases, the random settling technique differs from the others. Filtration and random settling preparation techniques were calibrated by spiking samples with microbeads. The ratio of microbeads observed in slides prepared using these two methods reflects bias due to loss of particles in the filtration technique. In addition, a hydrodynamic model for a fluttering and tumbling plate - such as F. profunda nannoliths - is proposed here along with calculated sinking velocities. These findings confirmed the efficiency of the long decantation time proposed for the random settling technique. The analysis of replicates, the validation with microbeads and the estimation of settling velocity of nannofossils in the tube convinced us that the higher relative abundance recorded by the random technique is not due to an imprecision of this method but, on the contrary, reflects the fact that it is more effective.
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| 6. |
- Lyssenko, Valeriya, et al.
(författare)
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Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes.
- 2007
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 117:8, s. 2155-2163
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants in the gene encoding for transcription factor-7-like 2 (TCF7L2) have been associated with type 2 diabetes (T2D) and impaired beta cell function, but the mechanisms have remained unknown. We therefore studied prospectively the ability of common variants in TCF7L2 to predict future T2D and explored the mechanisms by which they would do this. Scandinavian subjects followed for up to 22 years were genotyped for 3 SNPs (rs7903146, rs12255372, and rs10885406) in TCF7L2, and a subset of them underwent extensive metabolic studies. Expression of TCF7L2 was related to genotype and metabolic parameters in human islets. The CT/TT genotypes of SNP rs7903146 strongly predicted future T2D in 2 independent cohorts (Swedish and Finnish). The risk T allele was associated with impaired insulin secretion, incretin effects, and enhanced rate of hepatic glucose production. TCF7L2 expression in human islets was increased 5-fold in T2D, particularly in carriers of the TT genotype. Overexpression of TCF7L2 in human islets reduced glucose-stimulated insulin secretion. In conclusion, the increased risk of T2D conferred by variants in TCF7L2 involves the enteroinsular axis, enhanced expression of the gene in islets, and impaired insulin secretion.
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