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  • 1
    Electronic Resource
    Electronic Resource
    s.l. ; Stafa-Zurich, Switzerland
    Solid state phenomena Vol. 51-52 (May 1996), p. 561-566 
    ISSN: 1662-9779
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Insulin resistance ; insulin receptors ; catecholamines ; β-adrenergic receptors ; phaeochromocytoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of β-adrenergic stimulation on insulin binding was studied in human fat cells in vitro. Isoproterenol rapidly (∼ 5 min) reduced insulin binding through a β-adrenergic and dose-dependent mechanism. The reduced binding was enhanced by the addition of adenosine deaminase and was also elicited by the addition of dibutyryl cAMP. This effect was due to a decreased number of binding sites. The reduction was rapidly reversed by propranolol (t1/2 ∼ 10 min) and other β-adrenoreceptor blocking agents. Insulin binding was also measured in fat cells from 6 patients with a phaeochromocytoma. A significant negative correlation between tracer binding and the log value of total urinary catecholamine excretion was found (r=−0.821,p〈0.05). Mean tracer insulin binding was reduced about 30% as compared to cells from 16 carefully matched control subjects. Decreased insulin binding was again mainly attributable to a decreased number of binding sites. Thus, β-adrenergic stimulation, both in vitro and in vivo, leads to a decreased number of binding sites for insulin in human fat cells.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Human adipose tissue ; lipolysis ; noradrenaline ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study dose-response relationships of the effects of noradrenaline and insulin on fat cells of different sizes were performed. Adipose cells larger than 100 μm were more responsive (expressed as absolute effects) to the lipolytic action of noradrenaline as well as to the antilipolytic effect of insulin. This suggests that in the larger cells thecapacity, i. e. the sum of factors contributing to the ability to stimulate or inhibit the metabolic rates, was greater than in the smaller ones. In contrast thesensitivity to these agents, i.e. the readiness to respond, was not different between small and large cells. It is shown that the concentrations of insulin needed to obtain an antilipolytic effect is far below that needed to stimulate glucose incorporation. This discrepancy in insulin concentrations required may be due to binding of insulin to receptors with different affinity.
    Type of Medium: Electronic Resource
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  • 4
    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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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 12 (1976), S. 137-143 
    ISSN: 1432-0428
    Keywords: Adipose tissue ; insulin ; catecholamines ; glycolytic enzymes ; glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Specimens of human adipose tissue were cultured for one week with or without the addition of insulin. The basal as well as the noradrenaline-stimulated lipolysis were enhanced in the explants cultured with insulin, showing that the long-term effect of the hormone is lipolytic. However, an acute antilipolytic effect of insulin could be demonstrated in these explants in the subsequent short-term incubations. The basal rate of glucose incorporation into the lipids was enhanced in the explants cultured with insulin. When insulin was added in the short-term incubations these explants did not further respond to the hormone while this was the case with the explants cultured without insulin. Thus, it seems that prolonged exposure to insulin leads to a diminished acute effect of the hormone on glucose metabolism. However, the same explants responded to the antilipolytic effect showing that insulin was able to bind itself to the membrane. The activities of hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) were increased in large fat cells both in freshly excised tissue and in the cultured explants. However, the activity of phosphofructokinase (PFK) did not correlate with the cell size. The presence of insulin during the culture period enhanced the activities of G6PDH, PK, and LDH, while this was not found for HK or PFK. The data thus suggest that the metabolic capacity of human fat cells is enhanced by long-term exposure to insulin. Although enzyme induction could be shown for G6PDH, PK and LDH it seems unlikely that this is of importance for the increased rates of glucose metabolism in these explants since the rate-limiting enzymes, HK and PFK, were not increased. Most probably, then, this stimulating effect of insulin is exerted on the membrane and the rate of glucose transport.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Glucose counter-regulation ; hypoglycaemia ; Type 1 diabetes ; adrenaline ; glucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucose counter-regulation during insulin-induced hypoglycaemia was studied in Type 1 diabetic patients without evidence of autonomic neuropathy and compared with that of a non-diabetic control group. The glucose recovery rate following hypoglycaemia was delayed in the diabetic compared with the control subjects and this was most pronounced for the initial, rapid phase of glucose increase (glucose increase in 15 min, control: 1.1±0.1 versus 0.4±0.1 mmol/l; p〈0.01). The release of glucagon during hypoglycaemia was blunted in the diabetic patients (maximal plasma levels, control: 148±25 versus 70±10pg/ml; p〈 0.01). The adrenaline levels were also lower compared with the control subjects (maximal plasma levels, control: 7.23±1.21 versus 3.27±0.87 nmol/l; p〈0.05). To evaluate the importance of the blunted glucagon response for the delayed glucose compensation, glucagon was infused during the hypoglycaemia. Overall glucose recovery rate was improved but did not return to normal. Consequently impaired glucagon release in the diabetic patients cannot alone explain impaired glucoregulation; the lower adrenaline levels and/or an effect of the previous glucose levels per se on hepatic glucose production are probably also of importance.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Growth hormone ; insulin resistance ; glucose production ; glucose utilization ; dose response effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The insulin-antagonistic effect of growth hormone was characterized by infusing the hormone at three different infusion rates (6, 12 or 24 mU·kg−1·min−1) for one h in 11 healthy subjects. The insulin effect was measured with the euglycaemic clamp technique combined with D-(3-3H)-glucose infusion to evaluate glucose production and utilization. A control study with NaCl (154 mmol·l−1) infusion was also performed. The insulin levels during the clamps were similar in all studies (36±0.2 mU·l−1). Peak growth hormone levels were reached at 60 min (growth hormone 6mU·kg−1·h−1: 31±5; growth hormone 12 mU·kg−1·h−1: 52±4 and growth hormone 24 mU·kg−1·h−1: 102±8mU·l−1). The insulin-antagonistic effect of growth hormone started after ∼2 h, was maximal after 4–5 h (∼39% inhibition of glucose infusion rate between control and growth hormone 24 mU·kg−1·h−1) and lasted for 6–7 h after peak levels. The resistance was due to a less pronounced insulin effect both to inhibit glucose production and to stimulate glucose utilization. Growth hormone infusion of 12 mU·kg−1·h−1 induced a similar insulin-antagonistic effect as the higher infusion rate whereas 6 mU·kg−1·h−1 induced a smaller response with a duration of 1 h between 3–4 h after peak levels of growth hormone. The present study demonstrates that growth hormone levels similar to those frequently seen in Type 1 (insulin-dependent) diabetic patients during poor metabolic control or hypoglycaemia, have pronounced insulin-antagonistic effects. The effects starts after about 2–3 h, is maximal after 4–5 h and lasts for about 6–7 h. Both duration and inhibitory effect of growth hormone are related to the plasma levels, where a maximal effect is seen at about 50 mU·l−1 or higher.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Insulin diabetes mellitus ; gastrointestinal motility ; gastric emptying ; motilin ; hyperinsulinaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experimental euglycaemic hyperinsulinaemia (insulin levels 46±4 mU/l) impaired the postabsorptive gastrointestinal motility in healthy individuals; the effect being particularly pronounced in the upper gastrointestinal tract (stomach and proximal duodenum). The postprandial gastric emptying, measured with a standardized99mTc labelled meal, was also significantly delayed (t50 increased by 38% or 32 min). This was combined with a slower carbohydrate absorption (delay in peak blood glucose level about 40 min). Furthermore, during experimental hyperinsulinaemia higher blood glucose levels were seen at 120 min than at 60 min after food ingestion. This was not seen in any subject in the control study where only 0.9% NaCl was infused. Blood levels of the motility-stimulating hormone, motilin, were significantly lower during experimental hyperinsulinaemia. Thus, experimental hyperinsulinaemia impairs the gastrointestinal motility in both the postabsorptive and postprandial states. This effect is combined with a delayed carbohydrate absorption. Hyperinsulinaemia per se may thus lead to alterations in carbohydrate absorption and can also contribute to the gastrointestinal disturbances in diabetes. [Diabetologia (1995) 38: 79–85]
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Keywords Peroxovanadate ; insulin ; isoprenaline ; cAMP ; lipolysis ; glucose uptake ; tyrosine phosphorylation ; NIDDM ; adipocyte ; in vitro.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the effects of insulin and the stable peroxovanadate compound potassium bisperoxopicolinatooxovanadate (bpV(pic)), a potent inhibitor of phosphotyrosine phosphatases, on lipolysis and glucose uptake in subcutaneous adipocytes from 10 male patients with non-insulin-dependent diabetes mellitus (NIDDM) and 10 matched non-diabetic control subjects. Lipolysis stimulated by isoprenaline or the cAMP analogue, 8-bromo-cyclic AMP (8-br-cAMP), was reduced by approximately 40 % in NIDDM compared to control subjects. In both groups bpV(pic) exerted an antilipolytic effect that was similar to insulin (∼ 50 % inhibition). 14C-U-glucose uptake was dose-dependently increased by bpV(pic) treatment, but this effect and also that of insulin were impaired in NIDDM compared to control (bpV(pic) 1.6-fold vs 2.4-fold and insulin 2.2-fold vs 3.4-fold). Furthermore, low concentrations of bpV(pic) did not affect insulin-stimulated glucose uptake, although tyrosine phosphorylation of the insulin receptor β-subunit was clearly increased by bpV(pic). In conclusion, 1) β-adrenergic stimulation of lipolysis in vitro is attenuated in NIDDM adipocytes due to post-receptor mechanisms. 2) Both insulin and bpV(pic) decrease lipolysis and enhance glucose uptake in control as well as NIDDM adipocytes. The effect on glucose uptake, but not that on lipolysis, is impaired in NIDDM cells. 3) Peroxovanadate does not improve sensitivity and responsiveness to insulin in NIDDM adipocytes, showing that insulin-resistant glucose uptake in NIDDM is not overcome by phosphotyrosine-phosphatase inhibition and, thus, probably is not caused by impaired tyrosine phosphorylation events alone. [Diabetologia (1997) 40: 1197–1203]
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Keywords PKB/Akt ; PI3-kinase ; insulin action ; Type II diabetes ; GLUT-4.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To examine protein kinase B/Akt distribution and phosphorylation in response to insulin in different subcellular fractions of human fat cells from healthy subjects and subjects with Type II (non-insulin-dependent) diabetes mellitus. Methods. We prepared subcellular fractions of plasma membranes (PM), low density microsomes and cytosol and examined gene and protein expression as well as serine and threonine phosphorylation in response to insulin. Results. Protein kinase B/Akt mRNA as well as total protein kinase B/Akt protein in whole-cell lysate and cytosol were similar in both groups. Insulin increased protein kinase B/Akt translocation to the the plasma membrane about twofold [(p 〈 0.03) in non-diabetic cells but this effect was impaired in diabetic cells (∼ 30 %; p 〉 0.1)]. In both groups, protein kinase B/Akt threonine phosphorylation considerably increased in low density microsomes and cytosol whereas serine phosphorylation was predominant in the plasma membrane. Phosphatidylinositol-dependent kinase 1, which partially activates and phosphorylates protein kinase B/Akt on the specific threonine site, was predominant in cytosol but it was also recovered in low density microsomes. Serine phosphorylation in response to insulin was considerably reduced (50–70 %; p 〈 0.05) in diabetic cells but threonine phosphorylation was less reduced (∼ 20 %). Wortmannin inhibited these effects of insulin supporting a role for PI3-kinase activation. Conclusion/interpretation. Insulin stimulates a differential subcellular pattern of phosphorylation of protein kinase B/Akt. Furthermore, insulin-stimulated translocation of protein kinase B/Akt to the plasma membrane, where serine phosphorylation and full activation occurs, is impaired in Type II diabetes. Threonine phosphorylation was much less reduced. This discrepancy may be related to differential activation of phosphatidylinositol 3-kinase in the different subcellular compartments and phosphatidylinositol-dependent kinase 1 having high affinity for phosphatidylinositol phosphate 3. [Diabetologia (2000) 43: 1107–1115]
    Type of Medium: Electronic Resource
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