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91.
Denervation and outlet obstruction induce a net synthesis of contractile and cytoskeletal proteins in the urinary bladder of the male rat 总被引:4,自引:0,他引:4
The concentrations of the contractile proteins actin and myosin and the cytoskeletal protein desmin were determined in urinary bladders from normal rats, and from rats with bladder outlet obstruction or denervation. Ten days of obstruction or total denervation by bilateral removal of the pelvic ganglia resulted in an almost fourfold increase in bladder weight. Actin and myosin concentrations did not change significantly. The total amount of actin was 1624±235 g in the control bladder. In the obstructed and denervated bladders it increased significantly to 6277±648 g and 7671±835 g, respectively. The desmin/actin ratio was 0.237±0.012 in the control bladders, and increased significantly to 0.369±0.015 in the obstructed and 0.343±0.022 in the denervated bladders. Partial denervation by removal of the pelvic ganglion on one side only increased bladder weight by 52%, but did not increase the desmin/actin ratio. The content of actin in such bladders increased by 82%. Both obstruction (which increases the functional load of the detrusor muscle cells) and denervation (which produces bladder paralysis) are known to induce hypertrophy of the detrusor smooth muscle cells. The study shows that the desmin/actin ratio and the total amount of contractile proteins increase in response to the hypertrophy as such, and not to the work performed by the smooth muscle cells, and that the nerves have no trophic influence on the growth response. Also, even a limited lesion of the bladder innervation is associated with growth and a net increase in the amount of contractile proteins. 相似文献
92.
Anders Arner 《Pflügers Archiv : European journal of physiology》1982,395(4):277-284
Strips of intact and chemically skinned (Triton X-100) taenia coli were mounted for isometric and quick-release experiments at 23°C. Active force increased in repeated high-K+ induced contractures in the intact muscle. Stable maximal force was 313±24 mN/mm2 (n=6). The skinned preparations activated by Ca2+, at 2 mM Mg2+, 3.2 mM MgATP and ionic strength 0.085 M, gave half maximal force atpCa=5.62±0.4 and a maximal force (63±8 mN/mm2) atpCa=4.5 (20–25 of the control K+-responses prior to skinning but about 60% of the first K+-response). Force-velocity relations were obtained from intact muscles and from the same muscles chemically skinned and activated at optimal Ca2+. Maximal shortening velocity (V
max) was unaltered in the skinned preparation compared to the intact muscle (0.138±0.011 vs 0.140±0.006 L/s) indicating similar kinetics of actomyosin interaction. In the intact muscle a decrease inV
max was found when the Ca2+ concentration was reduced. Calmodulin (1M) increased Ca2+ sensitivity (by about 0.6 log units) of the skinned preparation but at optimal Ca2+ caused no alteration in isometric force orV
max
Apreliminary report of some of the results presented here was given at the Scandinavian Physiology Society Meeting in Århus, November 1981. Arner A, Hellstrand P (1982) Acta Physiol Scand (Abstract) 114: 38 A. 相似文献
93.
Lavebratt C Sengul S Gu HF Persson B Nordfors L Ostenson CG Efendic S Arner P Hoffstedt J Schalling M 《International journal of obesity (2005)》2005,29(12):1422-1428
OBJECTIVE: Proximal chromosome 10q26 was recently linked to waist/hip ratio in European and African-American families. The objective was to investigate whether genomic variation in chromosome 10q26.11 reflects variation in obesity-related clinical parameters in a Swedish population. DESIGN: Genetic association study of single-nucleotide polymorphisms (SNPs) in chromosome 10q26.11 and obesity-related clinical parameters was performed. Obesity was defined as body mass index (BMI) > or = 30 kg/m2. SUBJECTS: Swedish Caucasians comprising 276 obese and 480 nonobese men, 313 obese and 494 nonobese women, 177 obese and 163 nonobese patients with type 2 diabetes mellitus (T2DM), and 106 obese and 201 nonobese subjects with impaired glucose tolerance (IGT) patients. MEASUREMENTS: Genotypes of 11 SNPs at chromosome 10q26.11, and various obesity-related clinical parameters. RESULTS: Homozygosity of a common haplotype constructed by three SNPs, rs2185937, rs1797 and hCV1402327, covering an interval of 2.7 kb, was suggested to confer an increased risk for obesity of 1.5 among men (P = 0.043). The C allele frequency and homozygous genotype frequency of the rs1797 tended to be higher among obese compared to among nonobese men (P = 0.017 and 0.020, respectively). The distribution of BMI and diastolic blood pressure was higher among those with the C/C genotype (P = 0.022 and 0.0061, respectively). The obese and the nonobese groups were homogeneous over BMI subgroups with regard to rs1797 risk genotype distribution. There was no tendency for association between rs1797 and obesity among neither women nor T2DM nor IGT patients. CONCLUSION: We show support for association between proximal chromosome 10q26.11 and obesity among Swedish men but not women through the analysis of a haplotype encompassing 2.7 kb. 相似文献
94.
Daniel Eriksson Hogling Mikael Rydén Jesper Bäckdahl Anders Thorell Peter Arner Daniel P. Andersson 《Surgery for obesity and related diseases》2018,14(7):936-942
Background
Bariatric surgery such as Roux-en-Y gastric bypass (RYGB) remains the most effective treatment of obesity and associated co-morbidities. Body fat distribution associates with metabolic function.Objective
To investigate if preoperative body fat mass and distribution measured by dual-energy x-ray absorptiometry (DXA) predict weight loss and metabolic outcome after RYGB, and to compare predictive value of DXA with simple anthropometric measures.Setting
Four Swedish hospitals within the Stockholm area.Methods
Two hundred fifteen women scheduled for RYGB were included. Evaluations before and 2 years after RYGB included determination of insulin sensitivity by the homeostatic model assessment of insulin resistance, blood pressure, plasma lipids, and anthropometric measures, such as waist-to-hip-ratio and fat percentage estimated by formula. Body fat mass and distribution were determined by DXA.Results
Follow-up rate was 77.2% (n = 166). All clinical, anthropometric, and DXA measures were improved/reduced postsurgery (all P<.0001). Android/gynoid fat mass ratio and waist-to-hip-ratio predicted improved homeostatic model assessment of insulin resistance (P = .0028 and .0014), independently of body mass index and age. Body fat percentage, measured by DXA or estimated by formula, predicted percent weight loss (P<.0001 and .0083). Body mass index predicted percent weight loss and percent excess body mass index lost (P = .0022 and<.0001). DXA and anthropometric measures performed equally as predictors, except for DXA measured fat percentage that was slightly better than formula estimated.Conclusion
DXA provided predictive values similar to those by basic anthropometric measures, suggesting a limited additional value of preoperative DXA to predict metabolic improvement and weight loss after RYGB in women. 相似文献95.
Different aetiologies of Type 2 (non-insulin-dependent) diabetes mellitus in obese and non-obese subjects 总被引:7,自引:0,他引:7
Summary Insulin responses to intravenous glucose infusion and glucose utilization during hyperinsulinaemic euglycaemic clamp were determined in a large homogeneous group of 65-year-old male subjects. Twenty-eight had untreated Type 2 (non-insulin-dependent) diabetes mellitus and the remaining 44 control subjects had a normal glucose tolerance. Diabetic patients with abdominal obesity displayed peripheral insulin resistance in combination with defective insulin secretion, whereas non-obese diabetic patients showed only a secretory defect. Thus, Type 2 diabetes in obese and non-obese elderly male subjects may take two forms where the cause of hyperglycaemia differs. 相似文献
96.
J. R. Zierath J. N. Livingston Anders Thörne Jan Bolinder Signy Reynisdottir Fredrik Lönnqvist Peter Arner 《Diabetologia》1998,41(11):1343-1354
Summary Increased mobilization of non-esterified fatty acids (NEFA) from visceral as opposed to peripheral fat depots can lead to
metabolic disturbances because of the direct portal link between visceral fat and the liver. Compared with peripheral fat,
visceral fat shows a decreased response to insulin. The mechanisms behind these site variations were investigated by comparing
insulin action on NEFA metabolism with insulin receptor signal transduction through the insulin receptor substrate-1 (IRS-1)
pathway in omental (visceral) and subcutaneous human fat obtained during elective surgery. Insulin inhibited lipolysis and
stimulated NEFA re-esterification. This was counteracted by wortmannin, an inhibitor of phosphaditylinositol (PI) 3-kinase.
The effects of insulin on antilipolysis and NEFA re-esterification were greatly reduced in omental fat cells. Insulin receptor
binding capacity, mRNA and protein expression did not differ between the cell types. Insulin was four times more effective
in stimulating tyrosine phosporylation of the insulin receptor in subcutaneous fat cells (p < 0.001). Similarly, insulin was two to three times more effective in stimulating tyrosine phosphorylation of IRS-1 in subcutaneous
fat cells (p < 0.01). This finding could be explained by finding that IRS-1 protein expression was reduced by 50 ± 8 % in omental fat
cells (p < 0.01). In omental fat cells, maximum insulin-stimulated association of the p85 kDa subunit of PI 3-kinase to phosphotyrosine
proteins and phosphotyrosine associated PI 3-kinase activity were both reduced by 50 % (p < 0.05 or better). Thus, the ability of insulin to induce antilipolysis and stimulate NEFA re-esterification is reduced in
visceral adipocytes. This reduction can be explained by reduced insulin receptor autophosphorylation and signal transduction
through an IRS-1 associated PI 3-kinase pathway in visceral adipocytes. [Diabetologia (1998) 41: 1343–1354]
Received: 27 February 1998 and in revised form: 12 May 1998 相似文献
97.
Arner P 《Diabetes/metabolism research and reviews》2002,18(Z2):S5-S9
Insulin resistance is one of the key factors responsible for hyperglycaemia in type 2 diabetes and can result in a number of metabolic abnormalities associated with cardiovascular disease (insulin resistance syndrome), even in the absence of overt diabetes. The mechanisms involved in the development of insulin resistance are multifactorial and are only partly understood, but increased availability of free fatty acids (FFAs) is of particular importance for the liver and skeletal muscle. The role of FFAs in type 2 diabetes is most evident in obese patients who have several abnormalities in FFA metabolism. Because of a mass effect, the release of FFAs from the total adipose tissue depot to the blood stream is increased and the high concentration of circulating FFAs impairs muscle uptake of glucose by competitive inhibition. In upper-body obesity, which predisposes individuals to type 2 diabetes, the rate of lipolysis is accelerated in visceral adipose tissue. This results in a selective increase in FFA mobilisation to the portal vein, which connects visceral fat to the liver. A high 'portal' FFA concentration has undesirable effects on the liver, resulting in dyslipidaemia, hyperinsulinaemia, hyperglycaemia and hepatic insulin resistance. Recently, a new class of antidiabetic agents, the thiazolidinediones (TZDs) or 'glitazones' has been developed. A prominent effect of these agents is the lowering of circulating FFA levels and it is believed, but not yet proven, that this interaction with FFAs constitutes a major mechanism behind the glucose-lowering effect of the TZDs. 相似文献
98.
Summary Insulin dissociation from its receptors on isolated human fat cells was investigated using mono-125I-[Tyr A 14]-insulin. Fat cells were equilibrated with 0.05 pmol/ml of the radioligand and then transferred to a radioactive
free buffer. The rate of dilution-induced dissociation of bound labelled insulin was enhanced in the presence of native insulin
(1.7 nmol/ml), both at 24 °C and 37 °C and in both omental and subcutaneous adipocytes. The dissociation of radioactive insulin
was more rapid when fat cells were equilibrated with 0.15 than with 0.05 pmol/ml of radioactive insulin, both in the presence
or absence of an excess of native insulin. Thus, the presence of site-site interactions of the negative cooperativity type
among insulin receptors of human fat cells is demonstrated. 相似文献
99.
Jan
stman Peter Arner Peter Engfeldt Lars Kager 《Metabolism: clinical and experimental》1979,28(12):1198-1205
Omental fat cells were 30% smaller than those in subcutaneous regions. In omental fat cells with a mean diameter of 95 mu, the basal cAMP concentration was 50% lower, but the basal rate of glycerol release was three times as rapid as in subcutaneous (epigastric) fat cells of identical size. Added at maximal effective concentration, noradrenaline increased the level of cAMP and the rate of glycerol release more markedly in the omental than in the subcutaneous adipocytes, whereas the response to isopropyl noradrenaline was similar. Before starvation the lipolytic effects of noradrenaline and isopropyl noradrenaline, respectively, were identical in the two regions of subcutaneous adipose tissue investigated (femoral and hypogastric). The findings were well related to the tissue levels of cAMP induced by the two agents. During starvation noradrenaline and isopropyl noradrenaline increased the cAMP level and the rate of lipolysis in fat cells obtained from the hypogastric region, whereas noradrenaline decreased these parameters in femoral adipocytes. Starvation was associated with a more prominent inhibitory effect of phenylephrine on basal and isopropyl-noradrenaline-induced lipolysis in femoral than in hypogastric adipose tissue. In conclusion, differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response. 相似文献
100.
Aims/hypothesis The regulation of skeletal muscle lipolysis is not fully understood. In the present study, the effects of systemic and local noradrenaline administration on lipolysis and blood flow rates in skeletal muscle and adipose tissue were studied in vivo.Methods First, circulating noradrenaline levels were raised tenfold by a continuous i.v. infusion (n=12). Glycerol levels (an index of lipolysis) were measured in m. gastrocnemius and in abdominal adipose tissue using microdialysis. Local blood flow was determined with the 133Xe clearance technique and whole-body lipolysis rates assessed with a stable glycerol isotope technique ([2H5] glycerol). Second, interstitial glycerol levels in m. gastrocnemius, m. vastus and adipose tissue were measured by microdialysis during local perfusion with noradrenaline (10–8–10–6 mol/l) (n=10). Local blood flow was monitored with the ethanol perfusion technique.Results With regard to systemic noradrenergic stimulation, no change in fractional release of glycerol (difference between tissue and arterial glycerol) was seen in skeletal muscle. In adipose tissue it transiently increased twofold (p<0.0001), and the rate of appearance of glycerol in plasma showed the same kinetic pattern. Blood flow was reduced by 40% in skeletal muscle (p<0.005) and increased by 50% in adipose tissue (p<0.05). After noradrenaline stimulation in situ, a discrete elevation of skeletal muscle glycerol was registered only at the highest concentration of noradrenaline (10–6 mol/l) (p<0.05). Adipose tissue glycerol doubled already at the lowest concentration (10–8 mol/l) (p<0.05). In skeletal muscle a decrease in blood flow was seen at the highest noradrenaline concentrations (p<0.05).Conclusions/interpretation Lipolysis and blood flow rates are regulated differently in adipose tissue and skeletal muscle. Adipose tissue displays a high, but transient (tachyphylaxia) sensitivity to noradrenaline, leading to stimulation of both lipolysis and blood flow rates. In skeletal muscle, physiological concentrations of noradrenaline decrease blood flow but have no stimulatory effect on lipolysis rates. 相似文献