| 1. |
- Azouri, Kristian, et al.
(författare)
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Hotellrapport Stockholm
- 2011
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Rapport (populärvet., debatt m.m.)abstract
- Stockholm är Sveriges största stad och marknadsför sig som ”The Capital of Scandinavia”. De flesta resenärer som besöker Sverige åker till just Stockholm. År 2010 nådde Stockholms län 10 miljoner kommersiella övernattningar. Det är lätt att ta sig till Stockholm med både flyg, tåg, båt, bil och buss. Stockholm har ett brett utbud av kongress- och mässanläggningar. År 2009 var Stockholm den sjunde mest populära staden i världen att förlägga kongresser på. I dagsläget är Sverige på väg ur den lågkonjunktur som startade år 2008. Sveriges BNP och valuta är på väg att stabiliseras och stärkas. Regeringen har även lagt in ett förslag om att sänka tjänstemomsen inom hotell- och restaurangbranschen. I denna rapport har vi valt att avgränsa oss till ett eget utvalt område inom Stockholm. Detta område innefattar 143 hotell med 20 054 hotellrum.De prognoser vi gjort gällande staden Stockholm och segmenten affärsresenärer och fritidsresenärer pekar på en ökning av besökare till staden. Detta kommer resultera i att hotellens beläggning, snittpris och RevPAR kommer att öka framtill år 2013. Efter år 2013 tror vi att segmentet affärsresenärer kommer att minska något procentuellt och kurvan för belagda nätter kommer att stabiliseras. Dock tror vi att segmentet fritidsresenärer kommer att öka procentuellt efter år 2013 och antalet belagda hotellrum kommer att successivt öka mellan åren 2011 – 2015. Vi tror att snittpris och RevPAR kommer att sjunka på grund av att en fritidsresenär generellt sätt inte betalar lika mycket för ett hotellrum som en affärsresenär gör.
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| 2. |
- Heinonen, Suvi E, et al.
(författare)
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Animal Models of Diabetic Macrovascular Complications: Key Players in the Development of New Therapeutic Approaches.
- 2015
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Ingår i: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2015
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Forskningsöversikt (refereegranskat)abstract
- Diabetes mellitus is a lifelong, incapacitating metabolic disease associated with chronic macrovascular complications (coronary heart disease, stroke, and peripheral vascular disease) and microvascular disorders leading to damage of the kidneys (nephropathy) and eyes (retinopathy). Based on the current trends, the rising prevalence of diabetes worldwide will lead to increased cardiovascular morbidity and mortality. Therefore, novel means to prevent and treat these complications are needed. Under the auspices of the IMI (Innovative Medicines Initiative), the SUMMIT (SUrrogate markers for Micro- and Macrovascular hard end points for Innovative diabetes Tools) consortium is working on the development of novel animal models that better replicate vascular complications of diabetes and on the characterization of the available models. In the past years, with the high level of genomic information available and more advanced molecular tools, a very large number of models has been created. Selecting the right model for a specific study is not a trivial task and will have an impact on the study results and their interpretation. This review gathers information on the available experimental animal models of diabetic macrovascular complications and evaluates their pros and cons for research purposes as well as for drug development.
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| 3. |
- Mahdessian, Diana, et al.
(författare)
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Profiling the human cytoplasmic proteome.
- 2016
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Ingår i: Molecular Biology of the Cell. - : AMER SOC CELL BIOLOGY. - 1059-1524 .- 1939-4586. ; 27
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Medina, Anya, et al.
(författare)
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Early deficits in insulin secretion, beta cell mass and islet blood perfusion precede onset of autoimmune type 1 diabetes in BioBreeding rats
- 2018
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 61:4, s. 896-905
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Genetic studies show coupling of genes affecting beta cell function to type 1 diabetes, but hitherto no studies on whether beta cell dysfunction could precede insulitis and clinical onset of type 1 diabetes are available.Methods: We used 40-day-old BioBreeding (BB) DRLyp/Lyp rats (a model of spontaneous autoimmune type 1 diabetes) and diabetes-resistant DRLyp/+ and DR+/+ littermates (controls) to investigate beta cell function in vivo, and insulin and glucagon secretion in vitro. Beta cell mass was assessed by optical projection tomography (OPT) and morphometry. Additionally, measurements of intra-islet blood flow were performed using microsphere injections. We also assessed immune cell infiltration, cytokine expression in islets (by immunohistochemistry and qPCR), as well as islet Glut2 expression and ATP/ADP ratio to determine effects on glucose uptake and metabolism in beta cells.Results: DRLyp/Lyp rats were normoglycaemic and without traces of immune cell infiltrates. However, IVGTTs revealed a significant decrease in the acute insulin response to glucose compared with control rats (1685.3 +/- 121.3 vs 633.3 +/- 148.7; p < 0.0001). In agreement, insulin secretion was severely perturbed in isolated islets, and both first- and second-phase insulin release were lowered compared with control rats, while glucagon secretion was similar in both groups. Interestingly, after 5-7 days of culture of islets from DRLyp/Lyp rats in normal media, glucose-stimulated insulin secretion (GSIS) was improved; although, a significant decrease in GSIS was still evident compared with islets from control rats at this time (7393.9 +/- 1593.7 vs 4416.8 +/- 1230.5 pg islet-1 h-1; p < 0.0001). Compared with controls, OPT of whole pancreas from DRLyp/Lyp rats revealed significant reductions in medium (4.1 x 109 +/- 9.5 x 107 vs 3.8 x 109 +/- 5.8 x 107 μm3; p = 0.044) and small sized islets (1.6 x 109 +/- 5.1 x 107 vs 1.4 x 109 +/- 4.5 x 107 μm3; p = 0.035). Finally, we found lower intra-islet blood perfusion in vivo (113.1 +/- 16.8 vs 76.9 +/- 11.8 μl min-1 [g pancreas]-1; p = 0.023) and alterations in the beta cell ATP/ADP ratio in DRLyp/Lyp rats vs control rats.Conclusions/interpretation: The present study identifies a deterioration of beta cell function and mass, and intra-islet blood flow that precedes insulitis and diabetes development in animals prone to autoimmune type 1 diabetes. These underlying changes in islet function may be previously unrecognised factors of importance in type 1 diabetes development.
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| 5. |
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| 6. |
- Mendu, Suresh Kumar, et al.
(författare)
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Increased GABA(A) channel subunits expression in CD8(+) but not in CD4(+) T cells in BB rats developing diabetes compared to their congenic littermates
- 2011
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 48:4, s. 399-407
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Tidskriftsartikel (refereegranskat)abstract
- GABA (γ-aminobutyric acid), the main inhibitory neurotransmitter in the central nervous system is also present in the pancreatic islet β cells where it may function as a paracrine molecule and perhaps as an immunomodulator of lymphocytes infiltrating the pancreatic islet. We examined CD4(+) and CD8(+) T cells from diabetes prone (DR(lyp/lyp)) or resistant (DR(+/+)) congenic biobreeding (BB) rats for expression of GABA(A) channels. Our results show that BB rat CD4(+) and CD8(+) T cells express α1, α2, α3, α4, α6, β3, γ1, δ, ρ1 and ρ2 GABA(A) channel subunits. In CD8(+) T cells from DR(lyp/lyp) animals the subunits were significantly upregulated relative to expression levels in the CD8(+) T cells from DR(+/+) rats as well as from CD4(+) T cells from both DR(lyp/lyp) and DR(+/+) rats. Functional channels were formed in the T cells and physiological concentrations of GABA (100 nM) decreased T cell proliferation. Our results are consistent with the hypothesis that GABA in the islets of Langerhans may diminish inflammation by inhibition of activated T lymphocytes.
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| 7. |
- Regnell, Simon E., et al.
(författare)
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Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic BioBreeding rats
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes.
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| 8. |
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| 9. |
- Wiking, Mikaela, et al.
(författare)
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Drafting the intermediate filament proteome
- 2016
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Ingår i: Molecular Biology of the Cell. - : American society of cell biology. - 1059-1524 .- 1939-4586. ; 27
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Zduniak, Krzysztof, et al.
(författare)
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Immunohistochemical analysis of cannabinoid receptor 1 expression in steatotic rat livers
- 2016
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Ingår i: Experimental and Therapeutic Medicine. - : Spandidos Publications. - 1792-0981 .- 1792-1015. ; 11:4, s. 1227-1230
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Tidskriftsartikel (refereegranskat)abstract
- The primary aim of the present study was to determine the expression levels of cannabinoid receptor type 1 (CB1) in steatotic rat livers. The secondary aim was to clarify whether steatosis and inflammation are more marked in areas with increased CB1 overexpression. For ethical and economic reasons, the present study investigated tissue from archived liver blocks, which were obtained from 38 rats that had been euthanized during the course of previous research at the Karolinska Institute of the Karolinska University Hospital (Stockholm, Sweden) and Lund University (Malmö, Sweden). Liver tissue fixed in formalin and embedded in paraffin was used that had been sourced from 36 male Sprague Dawley rats (age, 7 weeks) and 2 rats (age, 180 days) lacking normal leptin receptors. The rat liver tissue was stained with antibodies against CB1 and counterstained with hematoxylin. The expression of CB1 and the number of cells overexpressing CB1 were determined. Steatosis was scored according to the Dixon scoring system. CB1 overexpression and steatosis were detected in hepatocytes from all 38 livers sampled. The expression of CB1 was more marked in hepatocytes localized next to portal triads. Near the central veins, the expression was significantly weaker. Steatosis was more marked in areas of increased CB1 overexpres with publications reporting that CB1 in hepatocytes increases lipogenesis and contributes to inflammation.
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| 11. |
- Åkesson, Lina, et al.
(författare)
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Decreased core temperature and Increased beta(3)-Adrenergic sensitivity in diabetes-prone BB rats
- 2007
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 9:4, s. 354-362
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes-prone (DP) congenic DR.lypllyp BioBreeding (BB) rats all develop Type I diabetes between 50 and 81 days of age, while DR. lyp/+ or DR.+/+ BB rats are diabetes resistant (DR). The DP rats display reduced weight gain prior to developing hyperglycemia, implying that metabolic events may precede diabetes onset. We tested the hypothesis that temperature measurements could serve as a physiological marker for the impending onset of hyperglycemia. Methods: Prior to the onset of hyperglycemia, brain, lower back, and intrascapular brown adipose tissue temperatures were analyzed by thermal signature analysis, , which measures infrared emission from tissues. A thermocoupled rectal probe measured core temperature. In addition we performed a beta 3-adrenergic receptor challenge test with the beta 3-adrenergic receptor agonist BRL37344. Results: DP rats displayed lower core temperature than DR rats prior to the onset of hyperglycemia. No temperature difference was detected in brain, lower back, or intrascapular brown adipose tissue between DP and DR rats. The beta 3-adrenergic challenge showed that the rate of temperature increase after administration of BRL37344 was significantly higher (0.005 +/- 0.002 degrees C/min) in DP than in DR rats (P = 0.044). Conclusions: These studies reveal that the prediabetic DP rats fail to maintain core temperature and that they display increased sensitivity to heat production induced by a beta 3-adrenergic receptor agonist. These studies suggest that body temperature as a measure of metabolic dysregulation is altered in the prediabetic DP rat prior to the onset of hyperglycemia.
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| 12. |
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| 13. |
- Åkesson, Lina, et al.
(författare)
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Increased Lipid Oxidation Heralds Diabetes Onset in DR.lyp/lyp Rats.
- 2008
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Ingår i: Experimental and Clinical Endocrinology & Diabetes. - : Georg Thieme Verlag KG. - 1439-3646 .- 0947-7349. ; 116, s. 475-480
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The BB rat model of type 1 diabetes exhibits altered body weight gain and body temperature regulation prior to hyperglycemia onset, implying the existence of as yet unidentified biomarkers of autoimmune processes that destroy pancreatic beta cells. To investigate this hypothesis, we compared the metabolic profile of diabetes-resistant DR.lyp/+ rats and their diabetes-prone, congenic DR.lyp/lyp littermates in the days leading up to diabetes onset. METHODS: Except for the Gimap5 mutation on chromosome 4, congenic DR.lyp/lyp rats are genetically identical to DR.lyp/+ littermates. They invariably develop hyperglycemia at 46-81 days of age, whereas DR.lyp/+ rats do not develop diabetes. In addition to daily food intake and body weight, indirect calorimetry was performed continuously on male DR.lyp/lyp and DR.lyp/+ rats (n=6/group) for 6-18 days to measure locomotor activity, VO (2), VCO (2) and RQ. RESULTS: DR.lyp/lyp rats exhibited a progressive decrease of RQ compared to DR.lyp/+ rats 0.005+/-0.001 units/day (p<0.005). Limiting the analysis to the six days prior to diabetes onset revealed a larger decrease of 0.007+/-0.002 units/day (p<0.001) in DR.lyp/lyp animals, whereas RQ of the DR.lyp/+ rats remained unchanged. This metabolic change occurred prior to hyperglycemia onset and was not associated with changes of any other parameter. CONCLUSIONS: Diabetes onset in DR.lyp/lyp rats is heralded by a progressive shift towards lipid oxidation relative to carbohydrate metabolism.
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| 14. |
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| 15. |
- Åkesson, Lina
(författare)
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Regulation of lipid metabolism in rat and 3T3-L1 adipocytes; Cross-talk between Insulin, the neuro-peptides PACAP/VIP and with B1-integrins
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 Diabetes is a disorder that increases globally, but mainly in the western world. One of the hallmarks of Type 2 diabetes is insulin resistance in the target tissues of insulin action (adipose tissue, liver and skeletal muscle). In addition, most patients with Type 2 diabetes are obese. Increased release of free fatty acids from the enlarged and/or dysfunctional adipose tissue is suggested to be a direct cause of insulin resistance. Understanding regulation of adipocyte metabolism and intracellular signaling is therefore of great importance for further understanding of the development and treatment of insulin resistance and Type 2 diabetes. Results presented in this thesis demonstrate that the neuro-peptide pituitary adenylate cyclase-activating polypeptide (PACAP) is able to act directly on adipocytes in dual manners, depending on the presence or absence of insulin. In the absence of insulin, PACAP is able to efficiently stimulate lipolysis in a protein kinase A (PKA)-dependent manner. However, when insulin is present, PACAP-induced lipolysis is abolished and PACAP switches to potentiate insulin-induced lipogenesis. Furthermore, the lipolytic effects mediated by PACAP and the related vasoactive intestinal polypeptide (VIP) were shown to be mediated by VPAC2-R, one of three PACAP/VIP receptors expressed on rat adipocytes. However, activation of VPAC1-R and VPAC2-R resulted in activation of PKA, although only VPAC2-R stimulation resulted in lipolysis. It is conceivable to hypothesize that lipolysis and lipogenesis might be mediated via different PACAP-receptors and that PACAP signaling pathways are able to stimulate independent pools of cAMP and PKA. The potential impact of β1-integrin activation on insulin signaling was also studied in this thesis. Most cells cannot survive unless they are properly connected to the extracellular matrix. It has been hypothesized that insulin and growth factor signaling is closely integrated. The preliminary results presented in this thesis indicate that β1-integrins may act to potentiate phosphorylation of insulin signaling components in 3T3-L1 adipocytes, but not in primary adipocytes. However, further studies in this matter are needed. Taken together, this thesis has contributed to further understanding of PACAP/VIP effects and the signaling mechanisms whereby these peptides exert their effects in adipocytes. Furthermore, the importance of cross-talk between the insulin signaling pathways and those elicited by G-protein coupled receptors (GPCRs) and integrins has been emphasized.
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| 16. |
- Åkesson, Lina, et al.
(författare)
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Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats
- 2011
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Ingår i: Metabolomics. - : Springer. - 1573-3882 .- 1573-3890. ; 7:4, s. 593-603
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Tidskriftsartikel (refereegranskat)abstract
- The clinical presentation of type 1 diabetes is preceded by a prodrome of beta cell autoimmunity. We probed the short period of subtle metabolic abnormalities, which precede the acute onset of diabetes in the spontaneously diabetic BB rat, by analyzing the serum metabolite profile detected with combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). We found that the metabolite pattern prior to diabetes included 17 metabolites, which differed between individual diabetes prone (DP) BB rats and their age and sex matched diabetes resistant (DR) littermates. As the metabolite signature at the 40 days of age baseline failed to distinguish DP from DR, there was a brief 10-day period after which the diabetes prediction pattern was observed, that includes fatty acids (e.g. oleamide), phospholipids (e.g. phosphocholines) and amino acids (e.g. isoleucine). It is concluded that distinct changes in the serum metabolite pattern predict type 1 diabetes and precede the appearance of insulitis in spontaneously diabetic BB DP rats. This observation should prove useful to dissect mechanisms of type 1 diabetes.
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| 17. |
- Åkesson, Lina, et al.
(författare)
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VPAC2-R Mediates the Lipolytic Effects of Pituitary Adenylate Cyclase-Activating Polypeptide/Vasoactive Intestinal Polypeptide in Primary Rat Adipocytes.
- 2005
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 146:2, s. 744-750
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are structurally and functionally related. Their actions have been shown to be mediated by three different receptor subtypes: PAC1-R, which has exclusive affinity for PACAP, and VPAC1-R and VPAC2-R, which have equal affinity for PACAP and VIP. We recently showed that PACAP38 induces lipolysis in rat adipocytes, and in the present study we examined whether VIP has similar effects and which of the three receptors mediates this PACAP/VIP action. We showed by RT-PCR that all three receptor subtypes are present in rat adipocytes. We demonstrated that VIP (1-100 nM), like PACAP38, stimulates lipolysis in isolated adipocytes, as determined by glycerol release. By a pharmacological approach, using antagonists and agonists specific for the receptor subtypes, we elucidated the mechanisms by which PACAP38 and VIP mediate their lipolytic effects. We found that antagonists of PAC1-R [PACAP(6-38)] and VPAC1-R (PG97-269) did not affect lipolysis induced by 0.1-100 nM PACAP38 or VIP, and that a VPAC1-R agonist [K15, R16, L27VIP(1-7) GRF(8-27)] did not affect lipolysis at 1-1000 nM. However, two different VPAC2-R agonists [Hexa-VIP(1-28) and Ro25-1553] clearly mimicked the lipolytic effect of PACAP38 and VIP. In addition, the VPAC2-R antagonist PG99-465 (100 nM) caused right-shifted dose-response curves of PACAP38- and VIP-induced lipolysis. These results therefore provide evidence that all three PACAP/VIP receptor subtypes are expressed in primary rat adipocytes, but that the VPAC2-R subtype is responsible for mediating the lipolytic effects induced by PACAP38 and VIP.
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