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  • insulin secretion  (5)
  • indoles  (4)
  • 1
    Electronic Resource
    Electronic Resource
    Peripheral and hepatic insulin sensitivity in subjects with impaired glucose tolerance (1995)
    Springer
    Diabetologia 38 (1995), S. 699-704 
    Details
    ISSN: 1432-0428
    Keywords: Key words Impaired glucose tolerance ; insulin sensitivity ; hepatic glucose output ; insulin secretion ; labelled infusion technique.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent evidence suggests that the postprandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion (Δ 0–10 min insulin area 7 Δ 0–10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2–19.4] vs 9.1 [2.6–14.5] mU · mmol−1; p 〈 0.01). During the clamp, circulating insulin (93 ± 8 [mean ± SEM] and 81 ± 10 mU · l−1) and glucagon (54 ± 4 and 44 ± 6 ng · l−1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78 ± 0.27 vs 4.47 ± 0.53 mg · kg−1· min−1; p 〈 0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38 ± 0.10 and 0.30 ± 0.18 mg · kg−1· min−1). Therefore, the main defects in subjects with impaired glucose tolerance are decreased first phase insulin secretion and peripheral non-oxidative glucose disposal, but hepatic glucose output shows normal responsiveness to insulin. [Diabetologia (1995) 38: 699–704]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401842
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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
    Basal and 24-h C-peptide and insulin secretion rate in normal man (1987)
    Springer
    Diabetologia 30 (1987), S. 16-21 
    Details
    ISSN: 1432-0428
    Keywords: C-peptide ; insulin secretion ; C-peptide pharmacokinetics ; insulin dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An understanding of the metabolic abnormalities rising from inappropriate insulin delivery in diabetic patients demands a knowledge of 24-h and basal insulin secretion rates in normal man. We have used biosynthetic human C-peptide to determine its kinetic parameters in 10 normal subjects and applied these to measurements of plasma concentrations in the same subjects to determine pancreatic secretion rate. Metabolic clearance rate measured by stepped primed infusion of biosynthetic human C-peptide at rates of 10, 19 and 26nmol/h was 4.7±0.7 (±SD) ml·kg−1·min−1, and was independent of infusion rate. Fractional clearance (T1/2, 26±3 min) and distribution volume (0.178±0.039 l/kg) were calculated from the decline in concentration after cessation of the highest rate infusion. Basal insulin secretion calculated from the C-peptide metabolic clearance rate and plasma concentrations for the period 02.00 to 07.00 hours was 1.3±0.4U/h. Over 24h total insulin secretion on a standard high carbohydrate diet was 63±15 U, calculated from the area under the C-peptide concentration curve. Basal insulin secretion, therefore, accounted for 50±8% of total insulin secretion. Although only 5.6±1.1% of C-peptide was detected in 24-h urine collections, urinary C-peptide excretion was significantly related to 24-h C-peptide secretion (r=0.74,p〈0.02).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01788901
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Peripheral and hepatic insulin sensitivity in subjects with impaired glucose tolerance (1995)
    Springer
    Diabetologia 38 (1995), S. 699-704 
    Details
    ISSN: 1432-0428
    Keywords: Impaired glucose tolerance ; insulin sensitivity ; hepatic glucose output ; insulin secretion ; labelled infusion technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent evidence suggests that the post-prandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion (Δ 0–10 min insulin area ÷Δ 0–10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2–19.4] vs 9.1 [2.6–14.5] mU·mmol−1; p〈0.01). During the clamp, circulating insulin (93±8 [mean±SEM] and 81±10 mU·l−1) and glucagon (54±4 and 44±6 ng·l−1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78±0.27 vs 4.47±0.53 mg·kg−1·min−1; p〈0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38±0.10 and 0.30±0.18 mg·kg−1·min−1). Therefore, the main defects in subjects with impaired glucose tolerance are decreased first phase insulin secretion and peripheral non-oxidative glucose disposal, but hepatic glucose output shows normal responsiveness to insulin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401842
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    Paper (German National Licenses)
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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    The effect of melatonin and other indole derivatives in maintaining ovulation in rats kept in continuous light and the influence of these indoles on HIOMT activity in the pineal gland (1982)
    Springer
    Journal of neural transmission 53 (1982), S. 305-314 
    Details
    ISSN: 1435-1463
    Keywords: Pineal gland ; continuous light ; ovulation ; indoles ; melatonin ; HIOMT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present study was to investigate whether the ovulation-maintaining effect of melatonin in rats, exposed to continuous light (LL), was also exerted by other pineal indoles which have been reported to influence the reproductive processes of mammals. The effect of 10μg melatonin was compared with that of similar amounts of either N-acetylserotonin, 5-methoxytryptophol, 5-methoxyindole-3-acetic acid, 5-hydroxytryptophol, 5-methoxytryptamine or 5-methoxytryptophan. All these compounds appeared to be significantly less effective than melatonin in preventing the effect of LL, ovulation being preserved in only 20–33 % of the rats investigated, with melatonin this percentage being 60–75%. Investigations were also carried out to assess the effect of these indole derivatives on HIOMT (hydroxyindole-O-methyl transferase) activity in synthesizing different 5-methoxyindoles in the abnormally influenced pineal gland due to LL. Melatonin, the compound the effect of which on ovarian cyclicity is strongest, stimulates 5-methoxytryptophol synthesis; while other less active compounds stimulate the synthesis of melatonin and inhibit that of O-acetyl-5-methoxytryptophol. The possibility that the effect of other indoles than melatonin on ovarian cyclicity might be due to stimulation of melatonin synthesis was considered. A possible functional relationship of the different indoles cannot be excluded.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01252041
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  • 7
    Electronic Resource
    Electronic Resource
    The inhibitory effect of 5-methoxytryptophol on ovarian weight, follicular growth and egg production of adult white leghorn hens (Gallus domesticus L.) (1973)
    Springer
    Journal of neural transmission 34 (1973), S. 159-169 
    Details
    ISSN: 1435-1463
    Keywords: Pineal ; indoles ; gonads ; chick
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Identical age, body weight, or initial comb size are not useful as parameters in analysing effects of pineal substances on the gonadal system of adult white leghorn hens. A combination, however, of the initial comb size with the frequency of oviposition proved to be an adequate parameter. Administration of 5-methoxytryptophol in increasing concentrations to adult hens shows an inhibitory effect on ovarian and follicular weight. This effect is not only realized by a decrease in organ weight, but also by a retardation of the rhythm as expressed in initial comb size units. As follicular growth is mainly dependent on a FSH/LH ratio in which the LH content is increased, the inhibitory effect may possibly be described to this relation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01244669
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  • 8
    Electronic Resource
    Electronic Resource
    Age-dependent effects of 5-methoxytryptophol and melatonin on testes and comb growth of the white leghorn (Gallus Domesticus L.) (1972)
    Springer
    Journal of neural transmission 33 (1972), S. 179-194 
    Details
    ISSN: 1435-1463
    Keywords: Pineal ; indoles ; gonads
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Testes weights of white leghorns of the same age or of equal body weight vary considerably. Experiments on the effects of pinealectomy, administration of pineal extracts or indolic compounds on the testes weights therefore require better parameters. Cockerels having a similar initial comb size prove to have testes of similar weights. Experiments using this parameter permit a more exact comparison of control and experimental animals. Administration of 5-methoxytryptophol and melatonin in increasing concentrations to juvenile, maturing and adult white leghorn males shows an age-dependent activity. In juvenile birds, the testes and comb growth are stimulated by 5-methoxytryptophol and melatonin, whereas in maturing and adult cocks both indolic compounds show an inhibitory effect. It appears that the effect of 5-methoxytryptophol is more specific than that of melatonin in juvenile as well as in maturing and adult white leghorns.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01245316
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  • 9
    Electronic Resource
    Electronic Resource
    The stimulatory effects of several concentrations of 5-methoxytryptophol on testicular growth in the white leghorn (Gallus domesticus L.) (1973)
    Springer
    Journal of neural transmission 34 (1973), S. 49-60 
    Details
    ISSN: 1435-1463
    Keywords: Pineal ; indoles ; gonads ; chick
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Concerning the gonads, the initial comb size in white leghorn cockerels proved to be a parameter which permits a more exact comparison of control and experimental animals, than the generally used parameters of identical age and/or body weight. As in literature contradictory results are described after injecting different concentrations of 5-methoxyindoles, it may be possible that these results can be explained by the parameters used. To analyse this, several concentrations of 5-methoxytryptophol were injected in increasing amounts in white leghorn cockerels, using the comb size as a parameter. In all experiments a stimulatory effect of 5-methoxytryptophol on testicular weight was observed. Administration of the smallest concentrations (0.1–3.5μg, exp. I, and 1.0–35μg, exp. II) showed an acceleration of the growing rhythm of the testes if compared with the control animals. With the comb size as a parameter it was possible to analyse the degree of stimulation in comb size units. Administration of 2.5–87.5μg (exp. III) and of 10–350μg (exp. IV) of 5-methoxytryptophol resulted also in a stimulatory activity on testicular growth; acceleration of the growing rhythm, however, now proved to be irregular and could not be compared with the growing pattern of the testes in the control animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01244826
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