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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 25 (2000), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Delta-aminolevulinic acid (ALA) is used for photodynamic therapy of basal cell carcinoma (BCC) as it is converted to protoporphyrin IX in tumour tissue. During illumination with 635 nm light a photochemical reaction takes place, singlet oxygen is generated and the tumour destroyed. In this study we used the microdialysis technique to quantify the concentration of ALA at a certain depth in tumour and healthy skin. The penetration ability of ALA was investigated as a function of time in BCCs (n = 14) and in normal skin (n = 4) after topical application. The microdialysis catheters were inserted intracutaneously and the depth position recorded by means of ultrasound. Microdialysate sample concentrations of amino acids and ALA were determined by high performance ion-exchange chromatography. A laser Doppler perfusion imager measured perfusion in the BCCs. The data show that the average depth of the microdialysis catheters was 0.5 mm. The interstitial ALA concentration in the BCCs increased from 0 to 3.1 mmol/L 15 min after application of ALA, whereas no measurable amounts of ALA were found in healthy skin. The blood perfusion was 2.5-fold increased in the BCCs. The interstitial levels of amino acids were not significantly changed during the ALA treatment. In summary, we found that ALA rapidly penetrates tumour skin. We conclude that microdialysis seems to be well suited for pharmacodynamic studies of ALA in skin.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 134 (1996), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In this study we aimed to validate the microdialysis technique for metabolic measurements in the dermal interstitial fluid. The abdominal and forearm skin was used for microdialysis in 15 healthy normal weight volunteers. The depth of the microdialysis catheter was assessed by ultrasound measurement. Structural impairment and blood flow were judged from biopsies and from laser Doppler measurements taken adjacent to the catheters. Dermal interstitial lactate and pyruvate concentrations were measured, under steady stale fasting conditions, after equilibrium calibration of each catheter in situ. The dermal Interstitial glucose concentration was estimated by means of the retrodialysis calibration method, which has previously not been evaluated for skin microdialysis. The mean catheter depth (± standard deviation) was 0.8 ± 0.3 mm. Small areas of localized bleeding, but no inflammatory reaction, was found surrounding the catheters. The perfusion in the microdialysis region was slightly increased (15–25%1. The lactate/pyruvate ratio (12 ±0.7) showed non–ischaemic values. The dermal interstitial lactate concentration was significantly higher (1171 ± 228μmol/l) than the plasma lactate (781 ± 180μmol/l), indicating an ongoing nonoxidative glucose metabolism. Retrodialysis calibration correctly estimated the dermal glucose level to be similar to that in plasma, which may indicate the usefulness of this calibration method for microdialysis studies of endogenous substrates in the dermal interstitial fluid.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Adipocytes ; insulin ; vanadate ; peroxovanadate ; glucose uptake ; lipolysis ; tyrosine kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Aqueous solutions of peroxovanadium (pV) compounds are potent insulin-mimics in various types of cell. Since chemical instability is a problem with these agents, we studied the insulin-like action in human fat cells of a stable pV complex, bpV(pic). It enhanced 14C-U-glucose uptake in a dose-dependent manner by approximately twofold which was slightly less than the effect of insulin (approximately threefold). The pV complex did not alter cell-surface insulin binding and submaximal concentrations did not influence cellular sensitivity to insulin action on glucose uptake. The bpV(pic) inhibited the lipolytic effect of isoprenaline to the same extent as insulin; however, when the cGMP-inhibitable low-Km phosphodiesterase (cGI-PDE) was blocked with the specific inhibitor OPC 3911, the antilipolytic effect of insulin, but not that of bpV(pic), was completely prevented. Moreover, when lipolysis was stimulated by the non-hydrolysable cAMP analogue N6-monobutyryl cAMP, bpV(pic), in contrast to insulin, maintained an antilipolytic effect. These findings indicate that bpV(pic) exerts its antilipolytic effect not only through cGI-PDE activation, similar to the effect of insulin, but also by means of other mechanisms. The tyrosine kinase activity of insulin receptors from human placenta was not altered by the pV compound itself, whereas bpV(pic) clearly enhanced insulin-stimulated activity. In contrast, in situ tyrosine phosphorylation of the insulin receptor Β-subunit as well as that of several other proteins was clearly increased in cells which were treated with bpV(pic), whereas vanadate only amplified insulin-stimulated tyrosine phosphorylation. In conclusion, bpV(pic) exerts powerful insulin-like effects in human fat cells and may be a new and potentially useful agent in the management of insulin-resistant states.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Vanadate ; peroxovanadate ; adipose cells ; lipolysis ; glucose transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vanadate and peroxovanadate were recently reported to exert maximal or even supramaximal (peroxovanadate) insulin-like effects in rat adipocytes. To evaluate the response in human cells, isolated human adipocytes were exposed to insulin or various concentrations of vanadate (0–10 mmol/l) or peroxovanadate (0–5 mmol/l). Neither vanadate nor peroxovanadate affected 125I-insulin binding and insulin sensitivity. Vanadate exerted no apparent effect on 14C-U-glucose uptake, whereas 0.1 mmol/l peroxovanadate exerted a full insulin-like response (p〈0.001). No additive response was observed by combining either vanadate or peroxovanadate with insulin. Peroxovanadate at 0.1 mmol/l was as effective as insulin in inhibiting isoproterenol-stimulated lipolysis. Neither peroxovanadate nor insulin-inhibited lipolysis stimulated by N6-monobutyryl-cAMP, an analogue which is not hydrolysed by the cAMP-phosphodiesterase. It is concluded that peroxovanadate, but not vanadate, elicits a full insulin-like response in human adipocytes.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 39 (1996), S. 613-614 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 33 (1990), S. 253-256 
    ISSN: 1432-0428
    Keywords: Adipose tissue ; lactate ; glucose metabolism ; microdialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Microdialysis of the abdominal subcutaneous tissue was performed in seven healthy normal weight subjects after an overnight fast and also after oral ingestion of 100 g glucose. The lactate concentration in the interstitial water was compared with that in the venous and arterialized plasma from the cubital veins. In the postabsorptive state the lactate concentration in the subcutaneous tissue (1128±72 μmol/l, mean±SEM) was significantly higher (p〈0.01) than that in both arterialized (722±72 μmol/l) and venous plasma (798±41 μmol/l). The oral glucose load further increased the lactate level in the subcutaneous tissue throughout the observation period of 2 h. The kinetics for the increase in the lactate concentration was not apparently different in blood or tissue. The highest lactate levels were 1798±173 umol/l in the subcutaneous tissue and 1199±150 μmol/l and 1275±123 μmol/l in arterialized and venous plasma, respectively. It is concluded that abdominal adipose tissue produces lactate both in the fasting state and after an oral glucose load. The data emphasize the importance of the adipose tissue as a significant source of lactate production in the body.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Vanadate ; insulin receptor ; insulin binding ; glucose transport ; insulin sensitivity ; tyrosine kinase activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this study was to elucidate the acute effects of vanadate on cell surface insulin binding and insulin sensitivity in rat adipocytes. The cells were preincubated at 37° for 20 min followed by energy depletion with potassium cyanide, extensive washing and 125I-insulin binding. The presence of vanadate or insulin during the preincubation period dose-dependently enhanced 125I-insulin binding to normal adipocytes (maximally 4–5-fold) through an increased number of binding sites without any change in receptor affinity. Submaximal concentrations of vanadate added together with insulin enhanced the cellular sensitivity to the effect of insulin to stimulate 3-O-methylglucose transport. Vanadate, but not insulin, was also capable of increasing insulin binding as well as insulin sensitivity in insulin-resistant cells (treatment with N6-monobutyryl cAMP or amiloride and adipocytes from obese, aging rats). There was a correlation between the effect of vanadate to augment insulin binding and its ability to enhance cellular insulin sensitivity. Thus, the data suggest that short-term vanadate treatment improves insulin sensitivity through enhanced receptor binding and that this occurs in both normal and insulin-resistant cells.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 39 (1996), S. 613-614 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Keywords Insulin resistance ; epinephrine ; microdialysis ; interstitial fluid ; blood flow ; rat.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Muscle glucose uptake and lactate release during β-adrenergic stimulation by epinephrine (epi) and β-adrenergic blockade by propranolol (prop) were investigated during an euglycaemic hyperinsulinaemic (30 pmol · kg–1· min–1) with or without added somatostatin (0.1 μg/min; pancreatic) clamp in female rats. To assess the interstitial insulin, glucose and lactate concentrations, microdialysis was done in the medial femoral muscle in both legs. The influence of muscle skeletal blood flow on interstitial insulin, glucose and lactate was examined with the microsphere technique, using 57Co-microspheres. Epinephrine decreased glucose infusion rate by about 75 % (p 〈 0.0001) and increased concentrations of interstitial glucose by about 35 % (p 〈 0.001) and lactate by about 65 % (p 〈 0.01). Plasma insulin concentration increased during β-adrenergic stimulation by about 25 % (p 〈 0.05) whereas the interstitial insulin concentration was unchanged. Muscle blood flow in the hindlimb was considerably enhanced by about 130 %, (p 〈 0.001) by epinephrine. Infusion of propranolol totally abolished all the above effects induced by epinephrine. The data show that insulin resistance and vasodilation induced by β-adrenergic stimulation with epinephrine is accompanied by increased interstitial glucose as well as lactate concentrations in muscle. The increased interstitial glucose concentration is the result of a decreased cellular uptake of glucose together with an increased capillary delivery of glucose by vasodilation. It is concluded that the severe cellular resistance to insulin induced by epinephrine could not be overcome either by the increased insulin secretion or by vasodilation. [Diabetologia (1998) 41: 1467–1473]
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Type 2 diabetes ; obesity ; physical training ; glucose tolerance ; insulin ; C-peptide ; glucose clamp ; insulin binding ; adipocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Obese subjects with normal glucose tolerance (n=55), and, in another study, a group of patients with Type 2 (non-insulin-dependent) diabetes (n=33), and controls (n=13) matched for body weight and age but with normal glucose tolerance, participated in an individualized physical training program for 3 months. Under controlled dietary conditions, metabolic studies were performed before and in steady state after the last exercise session after training in the subjects showing signs of physical training in VO2 max and heart rate measurements. No changes occurred in body weight, body cell mass, body fat or adipose tissue cellularity. Oral glucose tolerance was improved in the patients with diabetes mellitus only. In both diabetic and control subjects initially elevated C-peptide concentrations decreased, while low C-peptide values increased and which was particularly pronounced in diabetic subjects with subnormal values. Peripheral insulin values did not change. Glucose disposal rate measured with the glucose clamp technique was similar in diabetic patients and control subjects. An improvement was seen at both submaximal and maximal insulin levels in both groups, correlating with improvement in glucose tolerance in the diabetic subjects. No changes were found in adipocytes in insulin binding or the antilipolytic effect of insulin at submaximal insulin levels, but there was a normalization of a decreased glucose incorporation into triglycerides. These results indicate that both insulin secretion and effectiveness are altered by physical training in different ways in different clinical entities. They suggest that in insulin resistant conditions with high insulin secretion (as indicated by high C-peptide concentrations) the increased peripheral insulin sensitivity is followed by a decreased insulin secretion. This is not associated with an improvement of glucose tolerance. In Type 2 diabetes with low insulin secretion, an increased insulin secretion results from physical training, perhaps due to accompanying sensitization of the autonomic nervous system. Peripheral insulin concentrations are not altered, suggesting that the extra insulin produced is captured by the liver. This mechanism, as well as the improved peripheral insulin responsiveness seen in the whole body and also seen at the cellular level, probably both contribute to an improvement in glucose tolerance.
    Type of Medium: Electronic Resource
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