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A characteristic feature of primary Sjögren’s syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in pSS. We have previously investigated adipose tissue infiltration in SG biopsies from pSS patients and non-SS sicca controls. Our findings indicated the distinct incidence of adipose tissue replacement in pSS patients, where adipocytes were detected in interleukin (IL) 6 rich regions. We now aimed to examine the development of adipocytes in the SG microenvironment, and delineate their possible involvement in immune reactions. A microarray analysis was performed on SG from 6 pSS patients and 6 non-SS controls, where the expression levels of genes involved in adipose tissue development, inflammatory responses, and lymphoma development were assessed. Real-time PCR was carried out on SG from 14 pSS patients and 15 non-SS controls to account for IL6, IL10, and IL17 mRNA levels. Immunohistochemical staining of frozen SG tissue using IL17 was also conducted. Our results indicate signalling pathways identified in SG of pSS patients displayed genes leading to prominent adipose tissue development and reduced mitochondrial fatty acid beta-oxidation (ARID5B, OXCT1, BDH1, SOX8, HMGCS2, FTO, ECHS1, PCCA, ACADL and ACADVL), inflammatory responses (IL1R1, IL7R, IL10RA, IL15, IL18RAP, CCL2, CCL5, CCL22, CXCR6, CD14, and CD48), and lymphoma development via JAK-STAT signalling (STAT2, TYK2, EBI3, FAS, TNFRSF1B, MAP3K8, HMOX1, LTB, TNF, STAT1, and BAK1). Genes involved in interferon production and signalling were also detected (IRF1, IRF9, and IRF7), in addition to IL6, IL10, and IL17. Higher mRNA levels of IL6, IL17 and IL10 were observed in the SG of pSS patients compared to controls. Moreover, IL17 positive cells were detected mostly interstitially in the SG and around adipocytes, also within the focal infiltrates. In conclusion, adipocyte development seems to be more prominent in the SG of pSS patients, where adipose tissue replacement is also evident. Whether this is due to disease progression, or the repair process, remains to be investigated. Detection of IL17 positive adipocytes in the target organ suggests their involvement in immune reactions.  相似文献   
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Summary During prolonged heavy exercise a gradual upward drift in heart rate (HR) is seen after the first 10 min of exercise. This secondary rise might be caused by a reduction in stroke volume due to reduced filling of the heart, which is dependent upon both hemodynamic pressure and blood volume. Swimming and bicycling differ with respect to hydrostatic pressure and to water loss, due to sweating. Five subjects were studied during 90 min of bicycle exercise, and swimming the leg kick of free style. The horizontal position during swimming resulted in a larger cardiac output and stroke volume. After the initial rise in heart rate the secondary rise followed parallel courses in the two situations. The rises were positively related to the measured increments in plasma catecholamine concentrations, which continued to increase as exercise progresssed. The secondary rise in HR could not be explained by changes in plasma volume or in water balance, nor by changes in plasma [K]. The plasma volume decreased 5–6% (225–250 ml) within the first 5 to 10 min of exercise both in bicycling and swimming, but thereafter remained virtually unchanged. The sweat loss during bicycling was four times greater than during swimming; but during swimming the hydrostatic conditions induced a diuresis, so that the total water loss was only 25% less than during bicycling.  相似文献   
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GLP-1 does not acutely affect insulin sensitivity in healthy man   总被引:2,自引:1,他引:2  
Summary Previous studies have suggested that glucagon-like peptide-1 (GLP-1) (7–36 amide) may have the direct effect of increasing insulin sensitivity in healthy man. To evaluate this hypothesis we infused GLP-1 in seven lean healthy men during a hyperinsulinaemic (0.8 mU · kg−1 · min−1), euglycaemic (5 mmol/l) clamp. Somatostatin (450 μg/h) was infused to suppress endogenous insulin secretion, and growth hormone (3 ng · kg−1 · min−1) and glucagon (0.8 ng · kg−1 · min−1) were infused to maintain basal levels. GLP-1 (50 pmol · kg−1 · h−1) or 154 mmol/l NaCl (placebo) was infused after 3 h of equilibration, i.e. from 180-360 min. GLP-1 infusion resulted in GLP-1 levels of approximately 40 pmol/l. Plasma glucose, insulin, growth hormone, and glucagon levels were similar throughout the clamps. The rate of glucose infusion required to maintain euglycaemia was similar with or without GLP-1 infusion (7.69±1.17 vs 7.76±0.95 mg · kg−1 · min−1 at 150–180 min and 8.56±1.13 vs 8.55±0.68 mg · kg−1 · min−1 at 330–360 min) and there was no difference in isotopically determined hepatic glucose production rates (− 0.30±0.23 vs −0.16±0.22 mg · kg−1 · min−1 at 330–360 min). Furthermore, arteriovenous glucose differences across the forearm were similar with or without GLP-1 infusion (1.43±0.23 vs 1.8±0.29 mmol/l), (ANOVA;p>0.60, in all instances). In conclusion, GLP-1 (7–36 amide) administered for 3 h, leading to circulating levels within the physiological range, does not affect insulin sensitivity in healthy man.  相似文献   
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