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  • 1
    Electronic Resource
    Electronic Resource
    Insulin resistance due to hyperglycaemia: an adaptation protecting insulin-sensitive tissues (1997)
    Springer
    Diabetologia 40 (1997), S. S141 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051431
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Dissociation between insulin sensitivity of glucose uptake and endothelial function in normal subjects (1996)
    Springer
    Diabetologia 39 (1996), S. 1477-1482 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Blood flow ; nitric oxide ; vasodilatation ; endothelium.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin increases limb blood flow in a time- and dose-dependent manner. This effect can be blocked by inhibiting nitric oxide synthesis. These data raise the possibility that insulin resistance is associated with endothelial dysfunction. To examine whether endothelial function and insulin sensitivity are interrelated we quantitated in vivo insulin-stimulated rates of whole body and forearm glucose uptake at a physiological insulin concentration (euglycaemic hyperinsulinaemic clamp, 1 mU · kg–1· min–1 insulin infusion for 2 h) and on another occasion, in vivo endothelial function (blood flow response to intrabrachial infusions of sodium nitroprusside, acetylcholine, and N-monomethyl-l-arginine) in 30 normal male subjects. Subjects were divided into an insulin-resistant (IR) and an insulin-sensitive (IS) group based on the median rate of whole body glucose uptake (31 ± 2 vs 48 ± 1 μmol · kg–1· min–1, p 〈 0.001). The IR and IS groups were matched for age, but the IR group had a slightly higher body mass index, percentage of body fat and blood pressure compared to the IS group. The IR group also had diminished insulin-stimulated glucose extraction (p 〈 0.05) compared to the IS group, while basal and insulin-stimulated forearm blood flow rates were identical. There was no difference between the IR and IS groups in the forearm blood flow response to endothelium-dependent (acetylcholine and N-monomethyl-l-arginine) or -independent (sodium nitroprusside) vasoactive drugs. In conclusion, the ability of insulin to stimulate glucose uptake at physiological insulin concentrations and endothelium-dependent vasodilatation are distinct phenomena and do not necessarily coexist. [Diabetologia (1996) 39: 1477–1482]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050601
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    UDP-N-acetylglucosamine transferase and glutamine: fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues (1997)
    Springer
    Diabetologia 40 (1997), S. 76-81 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Hexosamines ; insulin ; glucose ; diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glutamine:fructose 6-phosphate amidotransferase (GFA) is rate-limiting for hexosamine biosynthesis, while a UDP-GlcNAc β-N-acetylglucosaminyltransferase (O-GlcNAc transferase) catalyses final O-linked attachment of GlcNAc to serine and threonine residues on intracellular proteins. Increased activity of the hexosamine pathway is a putative mediator of glucose-induced insulin resistance but the mechanisms are unclear. We determined whether O-GlcNAc transferase is found in insulin-sensitive tissues and compared its activity to that of GFA in rat tissues. We also determined whether non-insulin-dependent diabetes mellitus (NIDDM) or acute hyperinsulinaemia alters O-GlcNAc transferase activity in human skeletal muscle. O-GlcNAc transferase was measured using 3H-UDP-GlcNAc and a synthetic cationic peptide substrate containing serine and threonine residues, and GFA was determined by measuring a fluorescent derivative of GlcN6P by HPLC. O-GlcNAc transferase activities were 2–4 fold higher in skeletal muscles and the heart than in the liver, which had the lowest activity, while GFA activity was 14–36-fold higher in submandibular gland and 5–18 fold higher in the liver than in skeletal muscles or the heart. In patients with NIDDM (n = 11), basal O-GlcNAc transferase in skeletal muscle averaged 3.8 ± 0.3 nmol/mg · min, which was not different from that in normal subjects (3.3 ± 0.4 nmol/mg · min). A 180-min intravenous insulin infusion (40 mU/m2· min) did not change muscle O-GlcNAc transferase activity in either group. We conclude that O-GlcNAc transferase is widely distributed in insulin-sensitive tissues in the rat and is also found in human skeletal muscle. These findings suggest the possibility that O-linked glycosylation of intracellular proteins is involved in mediating glucose toxicity. O-GlcNAc transferase does not, however, appear to be regulated by either NIDDM or acute hyperinsulinaemia, suggesting that mass action effects determine the extent of O-linked glycosylation under hyperglycaemic conditions. [Diabetologia (1997) 40: 76–81]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050645
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus (1999)
    Springer
    Diabetologia 42 (1999), S. 406-412 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Leptin ; glucosuria ; energy balance ; glucose.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. To determine causes of weight gain during insulin therapy with and without metformin in Type II (non-insulin-dependent) diabetes mellitus. Methods. Twenty-six patients with Type II diabetes (body mass index 28 ± 1 kg/m2) were treated with insulin alone (n = 13) or insulin and with metformin (n = 13). Components of energy balance (basal metabolic rate, energy intake, glucosuria) were measured at 0 and 12 months. Results. Glycaemic control improved similarly in patients using (HbA1 c 10.5 ± 0.3 vs 7.6 ± 0.2 %, p 〈 0.001) and not using (10.2 ± 0.3 vs 7.8 ± 0.3 %, p 〈 0.001) metformin. The metformin group required 47 % less insulin than the group not using metformin (p 〈 0.001). Body weight increased by 3.8 ± 0.8 and 7.5 ± 1.6 kg (p 〈 0.05), respectively. Basal metabolic rate and glucosuria were similar at 0 and 12 months in both groups but the metformin group decreased energy intake by 1.12 ± 0.46 MJ/day, whereas it remained unchanged in the other group (0.15 ± 0.42 MJ/day). Changes in body weight and glycaemia were statistically significant independent determinants of basal metabolic rate. Their change in opposite directions explained why basal metabolic rate remained unchanged. Conclusion/interpretation. Improved glycaemia promotes weight gain by decreasing both basal metabolic rate and glucosuria. Use of metformin decreases weight gain by reducing energy intake and is therefore a useful adjunct to insulin therapy in patients with Type II diabetes. [Diabetologia (1999) 42: 406–412]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051172
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Methodological aspects, dose-response characteristics and causes of interindividual variation in insulin stimulation of limb blood flow in normal subjects (1995)
    Springer
    Diabetologia 38 (1995), S. 555-564 
    Details
    ISSN: 1432-0428
    Keywords: Hyperinsulinaemic clamp ; muscle ; blood flow ; venous occlusion plethysmography ; Doppler ultrasound ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To resolve some of the controversy regarding insulin regulation of blood flow, we performed in 20 normal subjects a) a reproducibility study of plethysmographic, Doppler ultrasound and laser Doppler blood flow measurements (n=7), b) a sequential insulin dose-response study with measurement of forearm (plethysmography), leg (Doppler ultrasound) and skin (laser Doppler) blood flow (n=12), and c) a sequential insulin dose-response study with comparison of forearm (plethysmography) and calf (plethysmography) blood flow (n=8). We also searched for factors which might explain the interindividual variation in the blood flow response to insulin. During sequential insulin infusions (2 h each, 61±2, 139±6, 462±15 mU/l), forearm blood flow increased by 17±6, 50±14 and 113±17% (p〈0.05 or less between steps), respectively. The increase at the 61±2 mU/l insulin concentration barely exceeded methodological variation (13±2%). In contrast to the continuous increase in blood flow, the glucose arterio venous difference reached its maximum (1.7±0.2 mmol/l) at the lowest 61±2 mU/l insulin concentration and remained constant thereafter. Forearm and calf blood flow responses to insulin were virtually identical when determined with plethysmography. In contrast, only a 27% increase was detected in femoral flow index as determined by Doppler ultrasound. Forearm blood flow (per forearm volume) was highly correlated with the relative forearm muscle content (mean 59±5%, range 24–81%) both basally (r=0.86, p〈0.001, n=12) and at all insulin concentrations (r=0.85–0.92, p〈0.001) indicating that the percent of forearm that is muscle explains 70–85% of interindividual variation in blood flow. In conclusion 1) physiological insulin concentrations stimulate glucose uptake mainly by increasing glucose extraction while supraphysiological insulin concentrations increase forearm glucose uptake predominantly via increases in blood flow. 2) The dose-response characteristics of insulin stimulation of forearm and calf blood flow are similar when determined with strain-gauge plethysmography. 3) Relative forearm muscle content is a key factor in determining both basal forearm blood flow and the interindividual variation in its response to insulin in normal subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400724
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    Paper (German National Licenses)
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  • 6
    Electronic Resource
    Electronic Resource
    Methodological aspects, dose-response characteristics and causes of interindividual variation in insulin stimulation of limb blood flow in normal subjects (1995)
    Springer
    Diabetologia 38 (1995), S. 555-564 
    Details
    ISSN: 1432-0428
    Keywords: Key words Hyperinsulinaemic clamp ; muscle ; blood flow ; venous occlusion plethysmography ; Doppler ultrasound ; blood pressure.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To resolve some of the controversy regarding insulin regulation of blood flow, we performed in 20 normal subjects a) a reproducibility study of plethysmographic, Doppler ultrasound and laser Doppler blood flow measurements (n = 7), b) a sequential insulin dose-response study with measurement of forearm (plethysmography), leg (Doppler ultrasound) and skin (laser Doppler) blood flow (n = 12), and c) a sequential insulin dose-response study with comparison of forearm (plethysmography) and calf (plethysmography) blood flow (n = 8). We also searched for factors which might explain the interindividual variation in the blood flow response to insulin. During sequential insulin infusions (2 h each, 61 ± 2, 139 ± 6, 462 ± 15 mU/l), forearm blood flow increased by 17 ± 6, 50 ± 14 and 113 ± 17 % (p 〈 0.05 or less between steps), respectively. The increase at the 61 ± 2 mU/l insulin concentration barely exceeded methodological variation (13 ± 2 %). In contrast to the continuous increase in blood flow, the glucose arterio venous difference reached its maximum (1.7 ± 0.2 mmol/l) at the lowest 61 ± 2 mU/l insulin concentration and remained constant thereafter. Forearm and calf blood flow responses to insulin were virtually identical when determined with plethysmography. In contrast, only a 27 % increase was detected in femoral flow index as determined by Doppler ultrasound. Forearm blood flow (per forearm volume) was highly correlated with the relative forearm muscle content (mean 59 ± 5 %, range 24–81 %) both basally (r = 0.86, p 〈 0.001, n = 12) and at all insulin concentrations (r = 0.85–0.92, p 〈 0.001) indicating that the percent of forearm that is muscle explains 70–85 % of interindividual variation in blood flow. In conclusion 1) physiological insulin concentrations stimulate glucose uptake mainly by increasing glucose extraction while supraphysiological insulin concentrations increase forearm glucose uptake predominantly via increases in blood flow. 2) The dose-response characteristics of insulin stimulation of forearm and calf blood flow are similar when determined with strain-gauge plethysmography. 3) Relative forearm muscle content is a key factor in determining both basal forearm blood flow and the interindividual variation in its response to insulin in normal subjects. [Diabetologia (1995) 38: 555–564]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400724
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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