| 1. |
- Andersson, Daniel P., et al.
(författare)
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Omentectomy in addition to gastric bypass surgery and influence on insulin sensitivity : A randomized double blind controlled trial
- 2014
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 33:6, s. 991-996
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Accumulation of visceral adipose tissue is associated with insulin resistance and cardio-vascular disease. The aim of this study was to elucidate whether removal of a large amount of visceral fat by omentectomy in conjunction with Roux en-Y gastric bypass operation (RYGB) results in enhanced improvement of insulin sensitivity compared to gastric bypass surgery alone. Methods: Eighty-one obese women scheduled for RYGB were included in the study. They were randomized to RYGB or RYGB in conjunction with omentectomy. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp before operation and sixty-two women were also reexamined 2 years post-operatively. The primary outcome measure was insulin sensitivity and secondary outcome measures included cardio-metabolic risk factors. Results: Two-year weight loss was profound but unaffected by omentectomy. Before intervention, there were no clinical or metabolic differences between the two groups. The difference in primary outcome measure, insulin sensitivity, was not significant between the non-omentectomy (6.7 +/- 1.6 mg/kg body weight/minute) and omentectomy groups (6.6 +/- 1.5 mg/kg body weight/minute) after 2 years. Nor did any of the cardio-metabolic risk factors that were secondary outcome measures differ significantly. Conclusion: Addition of omentectomy to gastric bypass operation does not give an incremental effect on long term insulin sensitivity or cardio-metabolic risk factors. The clinical usefulness of omentectomy in addition to gastric bypass operation is highly questionable.
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| 2. |
- Arner, Peter, et al.
(författare)
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Variations in the size of the major omentum are primarily determined by fat cell number
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:5, s. E897-E901
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Accumulation of visceral adipose tissue (VAT) is strongly linked to insulin resistance. Variations in the size of any adipose depot are determined by alterations in adipocyte volume and/or number. The individual contribution of each of the latter factors was determined in the major omentum, a fully resectable VAT depot.SUBJECTS: Total removal of the major omentum (omentectomy) was performed in conjunction with bariatric surgery in 55 obese patients. Tissue weight as well as mean adipocyte size and number in the omentum were determined. In subgroups, total VAT was estimated by computerized tomography (n = 17) or dual-energy x-ray absorptiometry (n = 34).RESULTS: The weight of the major omentum (on average 0.6 kg) correlated significantly with total VAT mass estimated by computerized tomography or dual-energy x-ray absorptiometry (r = 0.48-0.7; P < .01). Omental weight in relation to total body fat correlated with several features of the metabolic syndrome and inversely with serum-leptin (P < .001). Mean adipocyte size and total adipocyte number correlated strongly with omental weight (r = 0.6-0.8; P < .0001), irrespective of body mass index and total body fat mass, and accounted almost in total for interindividual variations in omental size. However, stepwise regression analysis demonstrated that adipocyte number was significantly (P < .0001) more important (62%) than adipocyte size (35%).CONCLUSION: The size of the major omentum is representative for VAT mass and correlates with a pernicious metabolic profile. Variations in omental weight are primarily determined by adipocyte number and to a lesser degree by adipocyte size, suggesting that increased VAT mass in obesity is predominantly dependent on adipocyte proliferation.
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| 3. |
- Abramsson, Alexandra, 1973, et al.
(författare)
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The zebrafish amyloid precursor protein-b is required for motor neuron guidance and synapse formation.
- 2013
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Ingår i: Developmental biology. - : Elsevier BV. - 1095-564X .- 0012-1606. ; 381:2, s. 377-88
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Tidskriftsartikel (refereegranskat)abstract
- The amyloid precursor protein (APP) is a transmembrane protein mostly recognized for its association with Alzheimer's disease. The physiological function of APP is still not completely understood much because of the redundancy between genes in the APP family. In this study we have used zebrafish to study the physiological function of the zebrafish APP homologue, appb, during development. We show that appb is expressed in post-mitotic neurons in the spinal cord. Knockdown of appb by 50-60% results in a behavioral phenotype with increased spontaneous coiling and prolonged touch-induced activity. The spinal cord motor neurons in these embryos show defective formation and axonal outgrowth patterning. Reduction in Appb also results in patterning defects and changed density of pre- and post-synapses in the neuromuscular junctions. Together, our data show that development of functional locomotion in zebrafish depends on a critical role of Appb in the patterning of motor neurons and neuromuscular junctions.
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| 4. |
- Arlock, Per, et al.
(författare)
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Excitation and contraction of cardiac muscle and coronary arteries of brain-dead pigs
- 2023
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Ingår i: FASEB BioAdvances. - : Wiley. - 2573-9832. ; 5:2, s. 71-84
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Tidskriftsartikel (refereegranskat)abstract
- Excitability and contraction of cardiac muscle from brain-dead donors critically influence the success of heart transplantation. Membrane physiology, Ca2+-handling, and force production of cardiac muscle and the contractile properties of coronary arteries were studied in hearts of brain-dead pigs. Cardiac muscle and vascular function after 12 h brain death (decapitation between C2 and C3) were compared with properties of fresh tissue. In both isolated cardiomyocytes (whole-cell patch clamp) and trabecular muscle (conventional microelectrodes), action potential duration was shorter in brain dead, compared to controls. Cellular shortening and Ca2+ transients were attenuated in the brain dead, and linked to lower mRNA expression of L-type calcium channels and a slightly lower ICa,L, current, as well as to a lower expression of phospholamban. The current–voltage relationship and the current above the equilibrium potential of the inward K+ (IK1) channel were altered in the brain-dead group, associated with lower mRNA expression of the Kir2.2 channel. Delayed K+ currents were detected (IKr, IKs) and were not different between groups. The transient outward K+ current (Ito) was not observed in the pig heart. Coronary arteries exhibited increased contractility and sensitivity to the thromboxane analogue (U46619), and unaltered endothelial relaxation. In conclusion, brain death involves changes in cardiac cellular excitation which might lower contractility after transplantation. Changes in the inward rectifier K+ channel can be associated with an increased risk for arrhythmia. Increased reactivity of coronary arteries may lead to increased risk of vascular spasm, although endothelial relaxant function was well preserved.
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| 5. |
- Arlock, Per, et al.
(författare)
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Ion currents of cardiomyocytes in different regions of the Göttingen minipig heart
- 2017
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Ingår i: Journal of Pharmacological and Toxicological Methods. - : Elsevier BV. - 1056-8719 .- 1873-488X. ; 86, s. 12-18
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The Göttingen minipig is a promising model for pharmacological safety assessment and for translational research in cardiology. We have examined the main ion currents in cardiomyocytes of the minipig heart. Methods Cardiac cells were isolated from different cardiac regions (endo-, mid- and epicardial left ventricle and right ventricle) from Göttingen minipigs and examined using the whole cell patch clamp technique combined with pharmacological interventions. Results The inward rectifier (IK1), the delayed rectifier (IK), with the rapid and slow components, (IKr, IKs) and the L-type Ca2 + channel (ICa,L) were identified in the different regions of the heart, whereas the Ca2 +-independent transient outward current (Ito1) was observed in only a few cells. IK1 was similar in the cardiac regions with a slightly lower value in the epicardial cells. IKs was smaller in epi- and endo-cardial regions. Discussion The equivalents of the main human cardiac ion currents are present in the minipig cardiomyocytes with the exception of the Ca2 +-independent Ito1. The study provides further evidence that the minipig is a valid model for investigating cardiovascular pharmacology.
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| 6. |
- Arner, Anders, et al.
(författare)
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Calcium transients and the effect of a photolytically released calcium chelator during electrically induced contractions in rabbit rectococcygeus smooth muscle
- 1998
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Ingår i: Biophysical Journal. - 1542-0086 .- 0006-3495. ; 75:4, s. 1895-1903
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Tidskriftsartikel (refereegranskat)abstract
- Intracellular Ca2+ was determined with the fura-2 technique during electrically induced contractions in the rabbit rectococcygeus smooth muscle at 22 degreesC. The muscles were electrically activated to give short, reproducible contractions. Intracellular [Ca2+] increased during activation; the increase in [Ca2+] preceded force development by approximately 2 s. After cessation of stimulation Ca2+ fell, preceding the fall in force by approximately 4 s. The fluorescence properties of fura-2 were determined with time-resolved spectroscopy using synchrotron light at the MAX-storage ring, Lund, Sweden. The fluorescence decay of free fura-2 was best described by two exponential decays (time constants approximately 0.5 and 1.5 ns) at low Ca2+ (pCa 9). At high Ca2+ (pCa 4.5), fluorescence decay became slower and could be fitted by one exponential decay (1.9 ns). Time-resolved anisotropy of free fura-2 was characteristic of free rotational motion (correlation time 0.3 ns). Motion of fura-2 could be markedly inhibited by high concentrations of creatine kinase. Time-resolved spectroscopy measurements of muscle fibers loaded with fura-2 showed that the fluorescence lifetime of the probe was longer, suggesting an influence of the chemical environment. Anisotropy measurements revealed, however, that the probe was mobile in the cells. The Ca2+-dependence of contraction and relaxation was studied using a photolabile calcium chelator, diazo-2, which could be loaded into the muscle cells in a similar manner as fura-2. Photolysis of diazo-2 leads to an increase in its Ca2+-affinity and a fall in free Ca2+. When muscles that had been loaded with diazo-2 were illuminated with UV light flashes during the rising phase of contraction, the rate of contraction became slower, suggesting a close relation between intracellular Ca2+ and the cross-bridge interaction. In contrast, photolysis during relaxation did not influence the rate of force decay, suggesting that relaxation of these contractions is not determined by the rate of Ca2+ removal or due to an increased Ca2+ sensitivity, but instead is limited by other processes such as deactivation by dephosphorylation or detachment of tension-bearing cross-bridges, possibly regulated by thin filament systems.
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| 7. |
- Arner, Anders, et al.
(författare)
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Intracellular calcium in hypertrophic smooth muscle from rat urinary bladder
- 2007
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 41:4, s. 270-277
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To explore whether infravesical outlet obstruction is associated with alterations in calcium activation of detrusor smooth muscle. Material and methods. Outlet obstruction was created by partial ligature of the urethra in female rats. Western blotting was performed using an antibody against the cytoplasmatic region of the alpha(1c) subunit of the L- type Ca2(+) channel. Intracellular calcium was measured using Fura-2 in detrusors that had been obstructed for 10 days and activated by high K+ concentrations at different extracellular Ca2(+) concentrations. The rate of force development after rapid opening of L- type Ca2(+) channels was measured in contractions initiated by flash photolysis of nifedipine in Ca2(+) containing depolarizing solution. Results. Bladder weight increased from 6293 to 254943 mg after 10 days of obstruction. Expression of the alpha(1c) subunit increased after 3 days and continued to increase until it was about fourfold greater after 10 days; however, it had not increased further at 6 weeks. This change was reversible after removal of obstruction. Activation with K+ produced a stable force at different extracellular Ca2(+) concentrations, with no difference in response between controls and rats that had been obstructed for 10 days. Intracellular Ca2(+) concentrations were lower in the obstructed group, showing that the calcium sensitivity of the contraction force had increased. The delay between the opening of L- type channels and the onset of contraction was longer in obstructed detrusors. Conclusions. Growth of detrusor muscle following obstruction is accompanied by attenuated calcium transients following activation, despite upregulation of L- type Ca2(+) channels. The Ca2(+) sensitivity of contraction was increased in obstructed detrusors. We suggest that the decreased surface: volume ratio in hypertrophic smooth muscle cells is partly involved in the lowered Ca2(+) transients. The increases in L- type calcium channels and in calcium sensitivity may be compensatory mechanisms.
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| 8. |
- Bamberg, Krister, et al.
(författare)
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Electrolyte handling in the isolated perfused rat kidney : demonstration of vasopressin V2-receptor-dependent calcium reabsorption
- 2020
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Ingår i: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 125:4, s. 274-280
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Tidskriftsartikel (refereegranskat)abstract
- Background The most profound effect of vasopressin on the kidney is to increase water reabsorption through V-2-receptor (V2R) stimulation, but there are also data suggesting effects on calcium transport. To address this issue, we have established an isolated perfused kidney model with accurate pressure control, to directly study the effects of V2R stimulation on kidney function, isolated from systemic effects. Methods The role of V2R in renal calcium handling was studied in isolated rat kidneys using a new pressure control system that uses a calibration curve to compensate for the internal pressure drop up to the tip of the perfusion cannula. Results Kidneys subjected to V2R stimulation using desmopressin (DDAVP) displayed stable osmolality and calcium reabsorption throughout the experiment, whereas kidneys not administered DDAVP exhibited a simultaneous fall in urine osmolality and calcium reabsorption. Epithelial sodium channel (ENaC) inhibition using amiloride resulted in a marked increase in potassium reabsorption along with decreased sodium reabsorption. Conclusions A stable isolated perfused kidney model with computer-controlled pressure regulation was developed, which retained key physiological functions. The preparation responds to pharmacological inhibition of ENaC channels and activation of V2R. Using the model, the dynamic effects of V2R stimulation on calcium handling and urine osmolality could be visualised. The study thereby provides evidence for a stimulatory role of V2R in renal calcium reabsorption.
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| 9. |
- Boberg, Lena, et al.
(författare)
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Signaling and metabolic properties of fast and slow smooth muscle types from mice
- 2018
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Ingår i: Pflügers Archiv. - : Springer. - 0031-6768 .- 1432-2013. ; 470:4, s. 681-691
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Tidskriftsartikel (refereegranskat)abstract
- This study aims to improve the classification of smooth muscle types to better understand their normal and pathological functional phenotypes. Four different smooth muscle tissues (aorta, muscular arteries, intestine, urinary bladder) with a 5-fold difference in maximal shortening velocity were obtained from mice and classified according to expression of the inserted myosin heavy chain (SMHC-B). Western blotting and quantitative PCR analyses were used to determine 15 metabolic and 8 cell signaling key components in each tissue. The slow muscle type (aorta) with a 12 times lower SMHC-B had 6-fold lower expression of the phosphatase subunit MYPT1, a 7-fold higher expression of Rhokinase 1, and a 3-fold higher expression of the PKC target CPI17, compared to the faster (urinary bladder) smooth muscle. The slow muscle had higher expression of components involved in glucose uptake and glycolysis (type 1 glucose transporter, 3 times; hexokinase, 13 times) and in gluconeogenesis (phosphoenolpyruvate carboxykinase, 43 times), but lower expression of the metabolic sensing AMP-activated kinase, alpha 2 isoform (5 times). The slow type also had higher expression of enzymes involved in lipid metabolism (hormone-sensitive lipase, 10 times; lipoprotein lipase, 13 times; fatty acid synthase, 6 times; type 2 acetyl-coenzyme A carboxylase, 8 times). We present a refined division of smooth muscle into muscle types based on the analysis of contractile, metabolic, and signaling components. Slow compared to fast smooth muscle has a lower expression of the deactivating phosphatase and upregulated Ca2+ sensitizing pathways and is more adapted for sustained glucose and lipid metabolism. © 2018 The Author(s)
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