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  • 1
    Electronic Resource
    Electronic Resource
    Differential binding of sulphated insulin to adipocytes and hepatocytes (1984)
    Springer
    Diabetologia 27 (1984), S. 184-188 
    Details
    ISSN: 1432-0428
    Keywords: Sulphated insulin ; adipocytes ; hepatocytes ; insulin ; receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The polymerization and precipitation of highly purified insulins which causes major problems in portable infusion systems does not occur with sulphated insulin. To compare the biological behaviour of sulphated insulin with that of a neutral highly purified monocomponent insulin, insulin receptor studies were performed on human and rat adipocytes and rat hepatocytes. Sulphated insulin displayed a lower affinity for binding to both human and rat adipocytes compared with neutral insulin, approximately four times the concentration being required to achieve half-maximal displacement of monoiodoinsulin (p〈0.05 and 0.01, respectively). A 20-fold higher concentration of sulphated insulin was required for half-maximal displacement from rat hepatocytes (p〈0.025). However, sulphated insulin bound to liver membranes with an affinity more closely resembling that for adipocytes rather than hepatocytes. Differences in the intracellular processing of the negatively charged insulin could account for the observed lower affinity of binding to hepatocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00273803
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  • 2
    Electronic Resource
    Electronic Resource
    Multiple metabolic abnormalities in normal glucose tolerant relatives of NIDDM families (1997)
    Springer
    Diabetologia 40 (1997), S. 1185-1190 
    Details
    ISSN: 1432-0428
    Keywords: Keywords C-peptide ; proinsulin ; insulin ; insulin secretion ; insulin resistance ; insulin clearance ; families ; adiposity ; glucose intolerance.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Non-diabetic first degree relatives of non-insulin-dependent diabetic (NIDDM) families are at increased risk of developing diabetes mellitus, and have been studied to identify early metabolic abnormalities. Hormone concentrations measured by specific enzyme immunoassays were assessed in non-diabetic relatives of North European extraction, and control subjects with no family history of diabetes were matched for age, sex and ethnicity. A 75-g oral glucose tolerance test was conducted and those with newly diagnosed NIDDM were excluded. Basal insulin resistance was determined by homeostasis model assessment (HOMA), and hepatic insulin clearance by C-peptide:insulin molar ratio. Relatives (n = 150) were heavier (BMI: p 〈 0.0001) than the control subjects (n = 152), and had an increased prevalence of impaired glucose tolerance (15 vs 3 %, p 〈 0.01). The relatives had increased fasting proinsulin levels and decreased C-peptide levels following the glucose load, while insulin levels were increased at all time points. To examine whether the differences in hormone levels were secondary to the differences in glucose tolerance and adiposity, we studied 100 normal glucose tolerant relatives and control subjects pair-matched for age, sex, waist-hip ratio and BMI. The differences in proinsulin levels were no longer apparent. However, the relatives remained more insulin resistant, and had decreased C-peptide levels and C-peptide:insulin ratios at all time points. In conclusion, we have identified several metabolic abnormalities in the normal glucose tolerant relatives, and propose that the decreased hepatic insulin clearance helps to maintain normoglycaemia in the face of combined insulin resistance and decreased insulin secretion. [Diabetologie (1997) 40: 1185–1190]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050805
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  • 3
    Electronic Resource
    Electronic Resource
    Comparative effects of phenformin, metformin and glibenclamide on metabolic rhythms in maturity-onset diabetics (1977)
    Springer
    Diabetologia 13 (1977), S. 145-152 
    Details
    ISSN: 1432-0428
    Keywords: Phenformin ; metformin ; glibenclamide ; blood glucose ; lactate ; alanine ; pyruvate ; ketone bodies ; maturity-onset diabetes ; diabetic control ; gluconeogenesis ; glycerol ; insulin ; triglycerides ; growth hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twelve hour metabolic rhythms have been performed on six maturity-onset diabetic subjects during successive periods of therapy with phenformin, metformin, and glibenclamide. Moderate control of blood glucose concentration was achieved with phenformin and metformin, the lowest concentrations being found with glibenclamide. Mean blood lactate concentration was grossly elevated during phenformin therapy, moderately elevated with metformin and normal during glibenclamide treatment. Similar patterns were found for the lactate/pyruvate ratio, alanine, glycerol and ketone bodies. Serum triglyceride concentrations were significantly higher during phenformin treatment than with the other two regimes. Serum insulin concentration was higher on glibenclamide than with either biguanide. Most of these effects of the biguanides could be accounted for by an inhibitory effect on hepatic gluconeogenesis. It is concluded that the use of biguanides as hypoglycaemic agents in diabetes is associated with the production of multiple metabolic abnormalities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00745143
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  • 4
    Electronic Resource
    Electronic Resource
    The metabolic response to hyperglycaemic clamping in insulin-dependent diabetes (1981)
    Springer
    Diabetologia 20 (1981), S. 113-117 
    Details
    ISSN: 1432-0428
    Keywords: Artificial endocrine pancreas ; glucose clamping ; hyperglycaemia ; insulin-dependent diabetes ; blood glucose ; ketone bodies ; alanine ; lactate ; pyruvate ; ketogenesis ; insulin ; glucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolic and hormonal effects of stable hyperglycaemia (10–12 mmol/l) have been examined in five insulin-dependent diabetics and compared with the results of 8 h (1200 to 2000 h) normoglycaemic (5–6 mmol/l) clamping. Glucose levels were maintained using a glucose controlled insulin infusion system. Mean blood lactate, pyruvate, total ketone bodies, glycerol and plasma nonesterified fatty acids were similar during the period of stable glycaemia at the two glucose levels. In contrast mean blood alanine was markedly elevated during hyperglycaemic clamping (0.384 ± 0.008 vs 0.298 ± 0.021 mmol/l) and 3-hydroxybutyrate was slightly decreased (0.068 ± 0.007 vs 0.084 ± 0.008 mmol/l). Plasma glucagon levels were raised during hyperglycaemic clamping and growth hormone slightly decreased. There was a close positive correlation between mean blood alanine and mean blood glucose (r = 0.79, p 〈 0.01), and a negative correlation of alanine with the amount of insulin infused (r =-0.72, p 〈 0.01). It is suggested that the raised alanine results from increased peripheral glucose utilisation. In general a short period of stable hyperglycaemia is not associated with a worsening of metabolic abnormalities in insulin-dependent diabetic subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00262012
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  • 5
    Electronic Resource
    Electronic Resource
    Failure of fasting to influence the GIP response to oral glucose in non-obese human subjects (1983)
    Springer
    Diabetologia 25 (1983), S. 372-374 
    Details
    ISSN: 1432-0428
    Keywords: GIP ; insulin ; glucose ; fasting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma GIP response to an oral 50 g glucose tolerance test has been compared in eight non-obese human subjects after 12 and 36 h of fasting. Basal plasma GIP and basal plasma insulin concentrations were similar after 12 and 36 h of fasting. Basal blood glucose was lower after 36 h fasting than after 12 h fasting (P〈0.0125). After 36 h fasting the oral glucose tolerance test stimulated higher blood glucose concentrations at 60, 90 and 120 min (p〈0.0125) and higher plasma insulin concentrations at similar time points (p〈0.05), but stimulated plasma GIP concentrations were similar after 12 and 36 h fasts. These findings show that the increased insulinotrophic effect of oral glucose after 36 h fasting in nonobese subjects is not due to an associated augmentation of the glucose-induced GIP response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253204
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  • 6
    Electronic Resource
    Electronic Resource
    Mechanism of anti-lipolytic action of acipimox in isolated rat adipocytes (1996)
    Springer
    Diabetologia 39 (1996), S. 45-53 
    Details
    ISSN: 1432-0428
    Keywords: Adipocytes ; acipimox ; lipolysis ; cyclic AMP ; cyclic AMP-dependent protein kinase ; hormone-sensitive lipase ; enzyme translocation ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Acipimox is commonly used to treat hyper-triglyceridaemia in non-insulin-dependent diabetic patients, but its precise mechanism of action has yet to be elucidated. We examined the in vitro effects of acipimox on the lipolytic regulatory cascade in epididymal adipocytes isolated from Wistar rats. Acipimox inhibited the lipolytic rate stimulated by adenosine deaminase (1 U/ml) in a concentration-dependent manner, reaching a near-basal value at 10 Μmol/l acipimox. Lipolysis activated by sub-maximal levels of isoproterenol in combination with adenosine deaminase (20 mU/ml) was significantly (p〈0.05) decreased by 100 Μmol/l acipimox, whereas, in the absence of adenosine deaminase, 100 Μmol/l acipimox showed no significant (p〉0.05) inhibition. These findings suggested that the anti-lipolytic mechanism regulated by adenosine may also be regulated by acipimox. Acipimox diminished the intracellular cyclic AMP level produced by 25 nmol/l isoproterenol in the presence of adenosine deaminase (20 mU/ml) in a concentration-dependent manner. At the same level of stimulation, acipimox inhibited the cyclic AMP-dependent protein kinase activity ratio and lipolytic rate over the same concentration range, with significant (p〈0.05) reductions occurring at and above, 0.5 Μmol/l and 10 Μmol/l acipimox, respectively. Western blotting showed that upon lipolytic stimulation (1 U/ml adenosine deaminase; 100 nmol/l isoproterenol) a threefold increase in the lipolytic rate was accompanied by a significant (p〈0.05) rise in hormone-sensitive lipase associated with the lipid fraction. Acipimox (1 mmol/l) and insulin (1 nmol/l) re-distributed hormone-sensitive lipase back to the cytosol, with a corresponding significant (p〈0.05) loss from the fat cake fraction of adipocyte homogenates. In conclusion, the anti-lipolytic action of acipimox is mediated through suppression of intracellular cyclic AMP levels, with the subsequent decrease in cyclic AMP-dependent protein kinase activity, leading to the reduced association of hormone-sensitive lipase with triacylglycerol substrate in the lipid droplet of adipocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400412
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  • 7
    Electronic Resource
    Electronic Resource
    Childhood size is more strongly related than size at birth to glucose and insulin levels in 10–11-year-old children (1997)
    Springer
    Diabetologia 40 (1997), S. 319-326 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Birth weight ; ponderal index ; glucose ; insulin ; children.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In adults low birthweight and thinness at birth are associated with increased risk of glucose intolerance and non-insulin-dependent diabetes mellitus. We have examined the relations between size at birth (birthweight, thinness at birth) and levels of plasma glucose and serum insulin in children, and compared them with the effects of childhood size. We performed a school-based survey of 10–11-year-old British children (response rate 64 %) with measurements made after an overnight fast. One group of children (n = 591) was studied fasting while the other (n = 547) was studied 30 min after a standard oral glucose load (1.75 g/kg). Serum insulin was measured by a highly specific ELISA method. Birthweight was assessed by maternal recall and thinness at birth using birth records. Neither fasting nor post-load glucose levels showed any consistent relationship with birthweight or ponderal index at birth. After adjustment for childhood height and ponderal index, both fasting and post-load insulin levels fell with increasing birthweight. For each kg increase in birthweight, fasting insulin fell by 16.9 % (95 % confidence limits 7.1–25.8 %, p = 0.001) and post-load insulin by 11.6 % (95 % confidence limits 3.5–19.1 %, p = 0.007). However, the proportional change in insulin level for a 1 SD increase in childhood ponderal index was much greater than that for birthweight (27.2 % and − 8.8 %, respectively, for fasting insulin). We conclude that low birthweight is not related to glucose intolerance at 10–11 years, but may be related to the early development of insulin resistance. However, in contemporary children obesity is a stronger determinant of insulin level and insulin resistance than size at birth. [Diabetologia (1997) 40: 319–326]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050681
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  • 8
    Electronic Resource
    Electronic Resource
    Metabolic effects of acute and prolonged growth hormone excess in normal and insulin-deficient man (1981)
    Springer
    Diabetologia 20 (1981), S. 123-128 
    Details
    ISSN: 1432-0428
    Keywords: Growth hormone ; insulin ; insulin deficiency ; glucagon ; blood glucose ; ketone bodies ; ketogenesis ; lipolysis ; non-esterified fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolic effects of acute (4 h) and prolonged (24 h) growth hormone excess at pathophysiological concentrations were studied by growth hormone administration to normal subjects with and without somatostatin induced insulin deficiency. Acute growth hormone excess produced mild hyperinsulinaemia, but blood glucose concentrations were unaltered whereas chronic growth hormone excess caused a small (0.5 mmol/l) but significant rise in overnight-fasting blood glucose concentration together with a similar rise in fasting insulin levels (Mean ± SEM 9 ± 1 v 4 ± 1 mU/l, p〈0.01). When insulin secretion was suppressed by somatostatin, a hyperglycaemic effect of acute growth hormone excess was unmasked, and the hyperglycaemic effect of chronic growth hormone excess was exaggerated. Acute growth hormone administration without somatostatin had a mild ketogenic action despite stimulated insulin secretion but no change in plasma non-esterified fatty acid or blood glycerol levels was observed. Somatostatin magnified the ketogenic effect of acute growth hormone excess, and unmasked a lipolytic action. Prolonged growth hormone excess had a lipolytic action that was increased by somatostatin, although the ketogenic effect of growth hormone was only seen during somatostatin induced insulin deficiency. The acute hyperglycaemic, lipolytic and ketogenic actions of growth hormone in normal subjects are limited by a compensatory rise in insulin secretion although with chronic exposure hyperglycaemic and lipolytic effects are seen. In insulin-deficient states, however, elevated growth hormone levels could be important in promoting hyperglycaemia and hyperketonaemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00262014
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  • 9
    Electronic Resource
    Electronic Resource
    The effect of portal and peripheral insulin delivery on carbohydrate and lipid metabolism in a miniature pig model of human IDDM (1997)
    Springer
    Diabetologia 40 (1997), S. 1125-1134 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type 1 diabetic model ; minipig ; streptozotocin ; portal vein ; insulin ; glucose clearance ; hepatic glucose production ; lipids.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A pig model of insulin-dependent diabetes was used to examine the importance of the portal-systemic insulin gradient for whole-body metabolic control. Six pigs had jugular vein, portal vein, and carotid artery cannulae implanted before being made diabetic (150 mg kg− 1 streptozotocin). Each animal received 4 weeks of portal and 4 weeks of peripheral insulin delivery in random order. The blood glucose target range was 5–10 mmol · l− 1, and serum fructosamine and fasting and postprandial blood glucose concentrations were not different between peripheral and portal insulin infusion. Insulin requirement was not different between the 4 week infusion periods, but fasting peripheral insulin levels after peripheral delivery (124 ± 16 (mean ± SEM) pmol · l− 1) were significantly higher (p 〈 0.05) than in portally infused (73.8 ± 5.4 pmol · l− 1) or pre-diabetic control animals (68.4 ± 3.6 pmol · l− 1). Basal hepatic glucose output was also higher (p 〈 0.05) in peripherally (4.2 ± 0.4 mg · kg− 1· min− 1) than in portally infused animals (2.9 ± 0.4 mg · kg− 1· min− 1) or controls (3.0 ± 0.3 mg · kg− 1· min− 1). Clamp glucose metabolic clearance rate was, however, not different between the peripheral and portal insulin delivery routes (8.1 ± 1.0 vs 9.0 ± 0.7 ml · kg− 1· min− 1), although both were significantly lower (p 〈 0.05) than that measured in prediabetic control animals (11.7 ± 1.0 ml · kg− 1· min− 1). Lipid profiles and subfractions were similar in all three groups. It is concluded that the portal route of delivery is superior to the peripheral in maintaining more appropriate insulin concentrations and control of hepatic glucose output, although in the absence of euglycaemia it is still associated with significant metabolic abnormalities. [Diabetologia (1997) 40: 1125–1134]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050797
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  • 10
    Electronic Resource
    Electronic Resource
    Twenty-four-hour insulin secretion rates, circulating concentrations of fuel substrates and gut incretin hormones in healthy offspring of Type II (non-insulin-dependent) diabetic parents: evidence of several aberrations (1999)
    Springer
    Diabetologia 42 (1999), S. 1314-1323 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Prediabetes ; physiological approach ; 24-h profile ; glucose ; insulin ; insulin secretion ; proinsulin ; non-esterified fatty acids ; gut incretin hormones ; intermediary metabolites.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Insulin resistance is a common feature in relatives of patients with Type II (non-insulin-dependent) diabetes mellitus and abnormalities in beta-cell function can also exist. Insight into non-fasting carbohydrate metabolism in these potentially prediabetic subjects relies almost exclusively on studies in which glucose is infused or ingested or both. We aimed to characterize insulin secretion and aspects of hormonal and metabolic patterns in relatives using a physiological approach. Methods. We examined profiles of insulin, C peptide, proinsulin, gut incretin hormones and fuel substrates in 26 glucose tolerant but insulin resistant (clamp) relatives and 17 control subjects during a 24-hour period including three meals. Results. During the day plasma glucose was slightly raised in relatives (p 〈 0.05). Overall insulin secretion calculated on the basis of C peptide kinetics were increased in relatives (p 〈 0.0005) whereas incremental insulin secretion after all three meals were similar. Peak incremental insulin secretion tended, however, to be reduced in relatives (p 〈 0.10). Despite considerably increased insulin concentrations in relatives (70 %, p 〈 0.001), serum NEFA did not differ. Postprandial proinsulin concentrations (p 〈 0.05), but not proinsulin:insulin ratios, were increased in relatives. After meals concentrations of glucose-dependent-insulinotropic polypeptide (p 〈 0.05) were increased in relatives. Glucagon-like peptide-1 concentrations were similar. Conclusion/interpretation. Several hormonal and metabolic aberrations are present in healthy relatives of Type II diabetic patients during conditions that simulate daily living. Increased concentrations of glucose-dependent-insulinotropic polypeptide could indicate a beta-cell receptor defect for glucose-dependent-insulinotropic polypeptide in the prediabetic stage of Type II diabetes. Incremental insulin secretion after mixed meals appear normal in relatives, although a trend towards diminished peak values possibly signifies early beta-cell dysfunction. [Diabetologia (1999) 42: 1314–1323]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051444
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