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  • 1
    ISSN: 1420-9071
    Keywords: Arbuscular mycorrhiza ; abscisic acid ; carotenoid ; Glomus ; nitrate reductase ; mycorradicin ; sterols ; yellow pigment in mycorrhiza
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract This communication compares some biochemical methods for quantifying colonization by arbuscular mycorrhizal (AM) fungi. The degree of mycorrhizal colonization can conveniently be measured by determining fungal specific sterols. AM-colonized plants show a specific synthesis of 24-methylene cholesterol and an enhanced level of campesterol (=24-methyl cholesterol). A gene probe for nitrate reductase, the key enzyme for nitrogen assimilation, has been developed, which allows the monitoring of the distribution of this enzyme in fungi. Among the phytohormones tested, only abscisic acid (ABA) is found at a considerably higher level in AM-colonized plants than in controls. The concentration of ABA is about twenty times higher in spores and hyphae of the AM fungusGlomus than in maize roots. Other phytohormones (auxins, cytokinins) do not show such alterations after mycorrhizal colonization. The roots of gramineous plants become yellow as a result of mycorrhizal colonization. The yellow pigment(s) formed is (are) deposited in larger quantities in the vacuole(s) of the root parenchyma and endodermis cells during the development of the gramineous plants. A substance isolated from such roots has now been identified as a C-14 carotenoid with two carboxylic groups, and named mycorradicin.
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  • 2
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; microalbuminuria ; glomerular filtration rate ; plasma lipoproteins ; insulin sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of simvastatin (10–20 mg/day) on kidney function, urinary albumin excretion rate and insulin sensitivity was evaluated in 18 Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria and moderate hypercholesterolaemia (total cholesterol ≥5.5 mmol·l−1). In a double-blind, randomized and placebo-controlled design treatment with simvastatin (n=8) for 36 weeks significantly reduced total cholesterol (6.7±0.3 vs 5.1 mmol·l−1 (p〈0.01)), LDL-cholesterol (4.4±0.3 vs 2.9±0.2 mmol·l−1 (p〈0.001)) and apolipoprotein B (1.05±0.04 vs 0.77±0.02 mmol·l−1 (p〈0.01)) levels as compared to placebo (n=10). Both glomerular filtration rate (mean±SEM) (simvastatin: 96.6±8.0 vs 96.0±5.7 ml·min−1·1.73 m−2, placebo: 97.1±6.7 vs 88.8±6.0 ml·min−1·1.73 m−2) (NS) and urinary albumin excretion rate (geometric mean x/÷ antilog SEM) (simvastatin: 18.4x/÷1.3vs 16.2 x/÷1.2 μg·min−1, placebo 33.1 x/÷ 1.3 vs 42.7 x/÷ 1.3 μg·min−1)(NS) were unchanged during the study. A euglycaemic hyperinsulinaemic clamp was performed at baseline and after 18 weeks in seven simvastatin-and nine placebo-treated patients. Isotopically determined basal and insulin-stimulated glucose disposal was similarly reduced before and during therapy in both the simvastatin (2.0±0.1 vs 1.9±0.1 (NS) and 3.1±0.6 vs 3.1±0.7 mg·kg−1·min−1 (NS)) and the placebo group (1.9±0.1 vs 1.8±0.1 (NS) and 4.1±0.6 vs 3.8±0.2 mg·kg−1·min−1 (NS)). No different was observed in glucose storage or glucose and lipid oxidation before and after treatment. Further, the suppression of hepatic glucose production during hyperinsulinaemia was not influenced by simvastatin (−0.7±0.8 vs −0.7±0.5 mg·kg−1·min−1 (NS)). In conclusion, despite marked improvement in the dyslipidaemia simvastatin had no impact on kidney function or urinary albumin excretion rate and did not reduce insulin resistance in these microalbuminuric and moderately hypercholesterolaemic Type 2 diabetic patients.
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  • 3
    ISSN: 1432-0428
    Keywords: Insulin resistance ; hyperinsulinaemia ; glucose tolerance ; chronic renal failure ; aerobic work capacity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tissue sensitivity to insulin and aerobic work capacity was measured in patients with mild to moderate progressive chronic renal failure. Twenty-nine non-diabetic patients with a glomerular filtration rate of 25 ml·min−1·1.73 m−2 (11–43) (median, range) and 15 sex, age, and body mass index matched control subjects with normal renal function were studied. Fasting blood glucose was comparable and in the non-diabetic range in the two groups as was the oral glucose tolerance test. Patients demonstrated hyperinsulinaemia both during fasting (p〈0.01) and during the test (p〈0.02). The tissue sensitivity to insulin, expressed by the amount of glucose infused during the last 60 min of a 120-min hyperinsulinaemia euglycaemic clamp (M-value) and the M/I ratio, was significantly lower in the patients than in the control subjects (M-value 404±118 vs 494±85 mg glucose/kg body weight, p〈0.02) (M/I ratio 1.77±0.71 vs 2.57±0.70 (mg/(kgBW·min) per pmol/l·100, p〈0.001). The maximal aerobic work capacity was significantly lower in the patients than in the control subjects (24±8 vs 32±11 ml O2/(kg body weight·min), p〈0.02) and positively correlated to the M-value and the M/I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting that these patients might benefit from physical training programmes.
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  • 4
    ISSN: 1432-0428
    Keywords: Substrate oxidation ; energy expenditure ; lipolysis ; ketogenesis ; “dawn” phenomenon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Growth hormone (GH) secretion is suppressed during insulin-like growth factor-I (IGF-I) administration. The aim of the study was to examine whether IGF-I alters the metabolic response to a GH pulse. Seven healthy male subjects (age 27±4 years, BMI 21.8±1.7 kg/m2) were treated with NaCl 0.9% (saline) or IGF-I (8 Μg · kg−1 · h−1) for 5 days by continuous subcutaneous infusion in a randomized, crossover fashion while receiving an isocaloric diet (30 kcal · kg−1 · day−1). On the third treatment day an intravenous bolus of 0.5 U GH was administered. Forearm muscle metabolism was examined by measuring arterialized and deep venous blood samples, forearm blood flow by occlusion plethysmography and substrate oxidation by indirect calorimetry. IGF-I treatment significantly reduced insulin concentrations by 80% (p〈0.02) and C-peptide levels by 78% (p〈0.02), as assessed by area under the curve. Non-esterified fatty acid (NEFA), glycerol and 3-OH-butyrate levels were elevated and alanine concentration decreased. Forearm blood flow rose from 2.10±0.43 (saline) to 2.79±0.37 ml · 100ml−1 · min−1 (IGF-I) (p〈0.02). GH-pulse: 10 h after i.v. GH injection serum GH peaked at 40.9±7.4 ng/ml. GH did not influence circulating levels of total IGFI, C-peptide, insulin or glucose, but caused a further increase in NEFA, glycerol and 3-OH-butyrate levels, indicating enhanced lipolysis and ketogenesis. This effect of GH was much more pronounced during IGF-I: NEFA rose from 702±267 (saline) and 885±236 (IGF-I) to 963±215 (saline) (p〈0.05) and 1815±586 Μmol/l (IGF-I) (p〈0.02), respectively; after 5 h, 3-OH-butyrate rose from 242±234 (saline) and 340±280 (IGF-I) to 678±638 (saline) (p〈0.02) and 1115±578 Μmol/l (IGF-I) (p〈0.02) respectively. After injection of GH, forearm uptake of 3-OH-butyrate was markedly elevated only in the subjects treated with IGF-I: from 44±195 to 300±370 after 20 min (p〈0.03) and to 287±91 nmol · 100 ml−1 · min−1after 120 min (p〈0.02). In conclusion, the lipolytic and ketogenic response to GH was grossly enhanced during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was increased.
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  • 5
    ISSN: 1432-0428
    Keywords: Glucose turnover ; forearm technique ; intermediary metabolites ; euglycaemic and hypoglycaemic glucose clamp ; indirect calorimetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary While it has very recently been reported that tumour induced hypoglycaemia is characterised by elevated production of insulin-like growth factor 2, the tissues responsible for induction of hypoglycaemia are largely unknown. We have investigated a patient with a large retroperitoneal mass and spontaneous hypoglycaemia. When compared to a reference population the patient displayed: (1) An increased glucose disposal rate and a five-fold elevation of forearm glucose uptake. (2) A decreased endogenous glucose production rate. (3) Decreased circulating levels of lipid intermediates. (4) Increased glucose oxidation and decreased lipid oxidation. (5) Low circulating levels of insulin-like growth factor 2 and insulin-like growth factor-binding protein-3 and normal levels of insulin-like growth factor 1. (6) Normal insulin sensitivity (euglycaemic glucose clamp). Blood concentrations of insulin, C-peptide, proinsulin, glucagon, growth hormone and catecholamines were within normal range, but the growth hormone response to hypoglycaemia was blunted. The data suggest that the mechanisms behind tumour induced hypoglycaemia are of systemic nature and that the tissue most prominently affected is striated muscle.
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  • 6
    ISSN: 1432-0428
    Keywords: Key words Diabetes ; diabetic neuropathy ; electrolytes ; hyperglycaemia ; nerve conduction ; somatostatin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insufficient metabolic control in diabetes mellitus is associated with a reversible reduction in nerve conduction velocity, but the mechanism behind this phenomenon is unknown. To examine the effect of acute hyperglycaemia on nerve conduction eight non-diabetic men (20–49 years of age) with no signs of peripheral neuropathy were studied before and after 3 h of hyperglycaemic clamping (plasma glucose ≈ 15 mmol/l), while insulin secretion was suppressed by somatostatin [Study 1]. Nerve conduction velocity, as determined in the proximal part of the median nerve, fell by 2.8 ± 3.0 m/s (2p-value: 0.033). However, during euglycaemic clamping (plasma glucose ≈ 5 mmol/l) in five non-diabetic men (19–38 years of age) infused solely with somatostatin [Study 2], a comparable decrement in nerve conduction velocity was found (1.7 ± 1.3 m/s, 2p-value: 0.043). In both studies relative hypoinsulinaemia was present. Serum-sodium decreased significantly (143 ± 1 mmol/l vs 137 ± 1 mmol/l [Study 1] and 143 ± 1 mmol/l vs 142 ± 2 mmol/l [Study 2]), while serum-potassium increased. In conclusion, the slight but significant reduction in nerve conduction velocity observed in both studies appears to be correlated to electrolyte changes. However, an effect of hypersomatostatinaemia or the hormonal changes associated with this cannot be excluded, while short-term hyperglycaemia per se seems to be without effect on nerve conduction velocity. [Diabetologia (1994) 37: 1216–1220]
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  • 7
    ISSN: 1432-0428
    Keywords: Keywords Insulin resistance ; relatives ; non-insulin-dependent diabetes mellitus ; oral glucose tolerance test ; physical fitness ; forearm blood flow ; muscle metabolism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary First degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM) are often reported to be insulin resistant. To examine the possible role of reduced physical fitness in this condition 21 first degree relatives of NIDDM patients and 22 control subjects without any history of diabetes were examined employing a 150-min hyperinsulinaemic (0.6 mU insulin · kg–1· min–1) euglycaemic clamp combined with the isotope dilution technique (3-3H-glucose, Hot GINF), the forearm technique and indirect calorimetry. During hyperinsulinaemia glucose disposal (Rd) and forearm glucose extraction were significantly diminished in the relatives (p 〈 0.01 and p 〈 0.05), but glucose oxidation and the suppressive effect on hepatic glucose production were normal. Arteriovenous differences across the forearm of the gluconeogenic precursors lactate, alanine and glycerol as well as the increments in forearm blood flow during hyperinsulinaemia were similar in the two groups. Maximal oxygen uptake (VO2 max) was lower in the relatives than in the control subjects (36.8 ± 1.9 vs 42.1 ± 2.0 ml · kg–1· min–1; p = 0.03). There was a highly significant correlation between Rd and VO2 max in both relatives and control subjects (r = 0.68 and 0.66, respectively; both p 〈 0.001). Comparison of the linear regression analyses of insulin-stimulated Rd on VO2 max in the two groups showed no significant differences between the slopes (0.10 ± 0.03 vs 0.09 ± 0.02) or the intercepts. In stepwise multiple linear regression analyses with insulin-stimulated Rd as the dependent variable VO2 max significantly determined the level of Rd (p 〈 0.01), whereas forearm blood flow and anthropometric data did not. In conclusion, the insulin resistance in healthy first degree relatives of patients with NIDDM is associated with a diminished physical work capacity. Whether, this finding is ascribable to environmental or genetic factors (e. g. differences in muscle fibre types, capillary density etc) remains to be determined. [Diabetologia (1996) 39: 813–822]
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  • 8
    ISSN: 1432-0428
    Keywords: Keywords Substrate oxidation ; energy expenditure ; lipolysis ; ketogenesis ; “dawn” phenomenon.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Growth hormone (GH) secretion is suppressed during insulin-like growth factor-I (IGF-I) administration. The aim of the study was to examine whether IGF-I alters the metabolic response to a GH pulse. Seven healthy male subjects (age 27 ± 4 years, BMI 21.8 ± 1.7 kg/m2) were treated with NaCl 0.9 % (saline) or IGF-I (8 μg · kg–1· h–1) for 5 days by continuous subcutaneous infusion in a randomized, crossover fashion while receiving an isocaloric diet (30 kcal · kg–1· day–1). On the third treatment day an intravenous bolus of 0.5 U GH was administered. Forearm muscle metabolism was examined by measuring arterialized and deep venous blood samples, forearm blood flow by occlusion plethysmography and substrate oxidation by indirect calorimetry. IGF-I treatment significantly reduced insulin concentrations by 80 % (p 〈 0.02) and C-peptide levels by 78 % (p 〈 0.02), as assessed by area under the curve. Non-esterified fatty acid (NEFA), glycerol and 3-OH-butyrate levels were elevated and alanine concentration decreased. Forearm blood flow rose from 2.10 ± 0.43 (saline) to 2.79 ± 0.37 ml · 100ml–1· min–1 (IGF-I) (p 〈 0.02). GH-pulse: 10 h after i. v. GH injection serum GH peaked at 40.9 ± 7.4 ng/ml. GH did not influence circulating levels of total IGF-I, C-peptide, insulin or glucose, but caused a further increase in NEFA, glycerol and 3-OH-butyrate levels, indicating enhanced lipolysis and ketogenesis. This effect of GH was much more pronounced during IGF-I: NEFA rose from 702 ± 267 (saline) and 885 ± 236 (IGF-I) to 963 ± 215 (saline) (p 〈 0.05) and 1815 ± 586 μmol/l (IGF-I) (p 〈 0.02), respectively; after 5 h, 3-OH-butyrate rose from 242 ± 234 (saline) and 340 ± 280 (IGF-I) to 678 ± 638 (saline) (p 〈 0.02) and 1115 ± 578 μmol/l (IGF-I) (p 〈 0.02) respectively. After injection of GH, forearm uptake of 3-OH-butyrate was markedly elevated only in the subjects treated with IGF-I: from 44 ± 195 to 300 ± 370 after 20 min (p 〈 0.03) and to 287 ± 91 nmol · 100 ml–1· min–1after 120 min (p 〈 0.02). In conclusion, the lipolytic and ketogenic response to GH was grossly enhanced during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was increased. [Diabetologia (1996) 39: 961–969]
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  • 9
    ISSN: 1432-0428
    Keywords: Type 1 diabetes mellitus ; Glucagon ; Hepatic glucose production
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of glucagon infusion on hepatic glucose production during euglycaemia was evaluated in seven Type 1 (insulin-dependent) diabetic patients and in ten control subjects. In the diabetic subjects normoglycaemia was maintained during the night preceding the study by a variable intravenous insulin and glucose infusion. During the study endogenous insulin secretion was suppressed by somatostatin (450 μg/h) and replaced by insulin infusion (0.15 mU·kg−1·min−1). 3H-glucose was infused for isotopic determination of glucose turnover. Plasma glucose was clamped at 5 mmol/1 for 2 h 30 min and glucagon (1.5 ng· kg−1·min−1) was then infused for the following 3 h. Hepatic glucose production and glucose utilisation were measured during the first, second and third hour of the glucagon infusion. Basal hepatic glucose production (just prior to glucagon infusion) was similar in diabetic (1.2±0.3 mg·kg−1·min−1) and control (1.6±0.1 mg·kg−1·min−1) subjects. In diabetic patients hepatic glucose production rose slowly to 2.1±0.5 mg·kg−1·min−1 during the first hours of glucagon infusion and stabilized at this level (2.4±0.5 mg·kg−1·min−1) in the third hour. In control subjects hepatic glucose production increased sharply to higher levels than in the diabetic subjects (3.4±0.3 mg·kg−1·min−1) during the first and second hour of glucagon infusion (p〈0.05) and then gradually fell (2.9±0.4 mg·kg−1·min−1) during the third hour. In conclusion, when stimulated with glucagon at a physiologic plasma concentration diabetic patients had 1) an overall reduced hepatic glucose production response and 2) an abnormal sluggish response pattern. These abnormalities may imply inappropriate counter-regulation following a hypoglycaemic episode.
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  • 10
    ISSN: 1432-0428
    Keywords: Insulin resistance ; Type 2 (non-insulin-dependent) diabetes mellitus ; hyperinsulinaemic clamp ; indirect calorimetry ; forearm glucose uptake ; muscle ; glycogen synthase ; insulin receptor kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin resistant glucose metabolism is a key element in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus. Insulin resistance may be of both primary (genetic) and secondary (metabolic) origin. Before and after diet-induced improvement of glycaemic control seven obese patients with newly-diagnosed Type 2 diabetes were studied with the euglycaemic clamp technique in combination with indirect calorimetry and forearm glucose balance. Muscle biopsies were obtained in the basal state and again after 3 h of hyperinsulinaemia (200 mU/l) for studies of insulin receptor and glycogen synthase activities. Similar studies were performed in seven matched control subjects. Insulin-stimulated glucose utilization improved from 110±11 to 183±23 mg·m−2·min−1 (p〈0.03); control subjects: 219+23 mg·m−2·min−1 (p=NS, vs post-diet Type 2 diabetes). Nonoxidative glucose disposal increased from 74±17 to 138+19 mg·m−2·min−1 (p〈0.03), control subjects: 159±22 mg· m−2·m−1 (p=NS, vs post-diet Type 2 diabetic patients). Forearm blood glucose uptake during hyperinsulinaemia increased from 1.58±0.54 to 3.35±0.23 μmol·l−1·min−1 (p〈0.05), control subjects: 2.99±0.86 μmol·l−1·min−1 (p=NS, vs post-diet Type 2 diabetes). After diet therapy the increase in insulin sensitivity correlated with reductions in fasting plasma glucose levels (r=0.97, p〈0.001), reductions in serum fructosamine (r=0.77, p〈0.05), and weight loss (r=0.78, p〈0.05). Values of muscle glycogen synthase sensitivity to glucose 6-phosphate (A0.5 for glucose 6-phosphate) were similar in the basal state. However, insulin stimulation of glycogen synthase was more pronounced after diet treatment (A0.5: 0.43±0.06 (before) vs 0.30±0.04 mmol/l (after); p〈0.03; control subjects: 0.22±0.03 mmol/l). Muscle insulin receptor binding and kinase activity were similar before and after diet treatment and comparable to values in the control group. The data suggest that impaired insulin stimulation of in vivo glucose turn-over and muscle glycogen synthase activity tend to be restored during successful diet treatment of patients with Type 2 diabetes.
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