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  • 1
    Electronic Resource
    Electronic Resource
    Demonstration of a relatively hepatoselective effect of covalent insulin dimers on glucose metabolism in dogs (1995)
    Springer
    Diabetologia 38 (1995), S. 1007-1013 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; insulin analogues ; glucose metabolism ; euglycaemic clamp ; insulin action ; hepatoselectivity ; glucose production
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin analogues with relatively greater effect on hepatic glucose production than peripheral glucose disposal could offer a more physiological approach to the treatment of diabetes mellitus. The fact that proinsulin exhibits this property to a minor degree may suggest that analogues with increased molecular size may be less able than insulin to obtain access to peripheral receptor sites. Covalent insulin dimers have previously been shown to possess lower hypoglycaemic potencies than predicted by their in vivo receptor binding affinities. Reduced rates of diffusion to peripheral target tissues-might be an explanation for the lower in vivo potency compared to insulin. To test the relative hepatic and peripheral effects of covalent insulin dimers, glucose clamp procedures with D-[3-3H] glucose tracer infusions were used in anaesthetised greyhounds to establish dose-response curves for rates of hepatic glucose production and glucose disposal with insulin, NαB1, NαB′ 1,-suberoyl-insulin dimer, and NεB29, NεB′ 29,-suberoyl-insulin dimer. With NαB1, NαB′ 1,-suberoyl-insulin dimer molar potencies relative to insulin were 68%, (34–133) (mean and 95% fiducial limits), for inhibition of hepatic glucose production and 14.7%, (10.3–20.9) for glucose disposal. With NεB29,NεB′ 29,-suberoyl-insulin dimer potencies were 75%, (31–184) and 2.5%, (1.5–4.3), for inhibition of hepatic glucose production and for glucose disposal, respectively. The demonstration that both dimers exhibit a significantly greater effect on glucose production than on glucose disposal supports the suggestion that analogues with increased molecular size may exhibit reduced ability to gain access to peripheral target cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402169
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in NIDDM (1995)
    Springer
    Diabetologia 38 (1995), S. 959-967 
    Details
    ISSN: 1432-0428
    Keywords: Very-low-density lipoprotein apolipoprotein B-100 ; non-insulin-dependent diabetes mellitus ; stable isotopes ; gas-chromatography mass-spectrometry ; mevalonic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We measured the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 (VLDL apoB) using a stable isotope gas-chromatography mass-spectrometry method in six patients with non-insulin-dependent diabetes mellitus (NIDDM) (four males, two females, age 57.5±2.2 years (mean±SEM), weight 88.2±5.5 kg, glycated haemoglobin (HbA1) 8.5±0.5%, plasma total cholesterol concentration 5.7±0.5 mmol/l, triglyceride 3.8±0.9 mmol/l, high-density lipoprotein (HDL) cholesterol 1.0±0.1 mmol/l) and six non-diabetic subjects matched for age, sex and weight (four males, two females, age 55.7±2.8 years, weight 85.8±5.6 kg, HbA1 6.5±0.1%, plasma total cholesterol concentration 5.7±0.5 mmol/l, triglyceride 1.2±0.1 mmol/l, HDL cholesterol 1.4±0.1 mmol/l). HbA1, plasma triglyceride and mevalpnic acid (an index of cholesterol synthesis in vivo) concentrations were significantly higher in the diabetic patients than in the non-diabetic subjects (p=0.006, p=0.02 and p=0.004, respectively). VLDL apoB absolute secretion rate was significantly higher in the diabetic patients compared with the non-diabetic subjects (2297±491 vs 921±115 mg/day, p〈0.05), but there was no significant difference in the fractional catabolic rate of VLDL apoB. There was a positive correlation between VLDL apoB secretion rate and (i) fasting C-peptide (r=0.84, p=0.04) and (ii) mevalonic acid concentration (r=0.83, p〈0.05) in the diabetic patients but not in the non-diabetic subjects. There was also a significant positive association between plasma mevalonic acid and plasma C-peptide (r=0.82, p〈0.05) concentrations in the diabetic patients. We conclude that in NIDDM, there is increased hepatic secretion of VLDL apoB which may partly explain the dyslipoproteinaemia seen in this condition. We suggest that increased secretion of this apolipoprotein may be a consequence of resistance to the inhibitory effect of insulin on VLDL apoB secretion. Insulin resistance may also be the mechanism by which cholesterol synthesis, a regulator of apoB secretion, is increased in NIDDM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400586
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Measurement of glucose metabolism and insulin secretion during normal pregnancy and pregnancy complicated by gestational diabetes (1996)
    Springer
    Diabetologia 39 (1996), S. 976-983 
    Details
    ISSN: 1432-0428
    Keywords: Gestational diabetes ; glucose metabolism ; insulin secretion ; intravenous glucose tolerance test ; minimal model ; pregnancy ; stable isotope
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Gestational diabetes affects 2–3% of pregnant women and is associated with foetal complications including macrosomia and an increased likelihood of developing diabetes in later life. We have therefore studied seven women with gestational diabetes and five control women both during the third trimester of pregnancy and again 2–3 months post-partum, using the minimal model analysis of the frequently sampled labelled ([6, 6-2H2]-glucose) intravenous glucose tolerance test. Glucose tolerance (glucose Kd) was significantly reduced in the women with gestational diabetes compared with the normal pregnant women both in pregnancy (1.16±0.11 vs 1.78±0.23%/min; p〈0.05) and post-partum (1.47±0.22 vs 2.59±0.43%/min; p〈0.05) and increased significantly in the control women after delivery (p〈0.05). Glucose effectiveness was not significantly different between the women with gestational diabetes and the control group either during or after pregnancy. Insulin sensitivity was significantly lower during pregnancy than after delivery in the women with gestational diabetes (p〈0.05). There was no significant difference in basal insulin secretion in the two groups during pregnancy or post-partum. However, during pregnancy the control subjects significantly increased (p〈0.001) their insulin secretion over a period of 20 min in response to an intravenous glucose tolerance test (96.2±42.7 pmol/kg) compared with post-partum values (58.3±25.2 pmol/kg) while in the women with gestational diabetes insulin secretion was similar in pregnancy (65.5±9.3 pmol/kg) and after delivery (57.7±15.7 pmol/kg). These data suggest that the glucose intolerance in gestational diabetes compared to normal pregnancy is due to reduced insulin sensitivity and an impaired ability in gestational diabetes to increase insulin secretion in response to glucose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403918
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in NIDDM (1995)
    Springer
    Diabetologia 38 (1995), S. 959-967 
    Details
    ISSN: 1432-0428
    Keywords: Key words Very-low-density lipoprotein apolipoprotein B-100 ; non-insulin-dependent diabetes mellitus ; stable isotopes ; gas-chromatography mass-spectrometry ; mevalonic acid.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We measured the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 (VLDL apoB) using a stable isotope gas-chromatography mass-spectrometry method in six patients with non-insulin-dependent diabetes mellitus (NIDDM) (four males, two females, age 57.5 ± 2.2 years (mean ± SEM), weight 88.2 ± 5.5 kg, glycated haemoglobin (HbA1) 8.5 ± 0.5 %, plasma total cholesterol concentration 5.7 ± 0.5 mmol/l, triglyceride 3.8 ± 0.9 mmol/l, high-density lipoprotein (HDL) cholesterol 1.0 ± 0.1 mmol/l) and six non-diabetic subjects matched for age, sex and weight (four males, two females, age 55.7 ± 2.8 years, weight 85.8 ± 5.6 kg, HbA1 6.5 ± 0.1 %, plasma total cholesterol concentration 5.7 ± 0.5 mmol/l, triglyceride 1.2 ± 0.1 mmol/l, HDL cholesterol 1.4 ± 0.1 mmol/l). HbA1, plasma triglyceride and mevalonic acid (an index of cholesterol synthesis in vivo) concentrations were significantly higher in the diabetic patients than in the non-diabetic subjects (p = 0.006, p = 0.02 and p = 0.004, respectively). VLDL apoB absolute secretion rate was significantly higher in the diabetic patients compared with the non-diabetic subjects (2297 ± 491 vs 921 ± 115 mg/day, p 〈 0.05), but there was no significant difference in the fractional catabolic rate of VLDL apoB. There was a positive correlation between VLDL apoB secretion rate and (i) fasting C-peptide (r = 0.84, p = 0.04) and (ii) mevalonic acid concentration (r = 0.83, p 〈 0.05) in the diabetic patients but not in the non-diabetic subjects. There was also a significant positive association between plasma mevalonic acid and plasma C-peptide (r = 0.82, p 〈 0.05) concentrations in the diabetic patients. We conclude that in NIDDM, there is increased hepatic secretion of VLDL apoB which may partly explain the dyslipoproteinaemia seen in this condition. We suggest that increased secretion of this apolipoprotein may be a consequence of resistance to the inhibitory effect of insulin on VLDL apoB secretion. Insulin resistance may also be the mechanism by which cholesterol synthesis, a regulator of apoB secretion, is increased in NIDDM. [Diabetologia (1995) 38: 959–967]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400586
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Measurement of glucose metabolism and insulin secretion during normal pregnancy and pregnancy complicated by gestational diabetes (1996)
    Springer
    Diabetologia 39 (1996), S. 976-983 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Gestational diabetes ; glucose metabolism ; insulin secretion ; intravenous glucose tolerance test ; minimal model ; pregnancy ; stable isotope.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Gestational diabetes affects 2–3 % of pregnant women and is associated with foetal complications including macrosomia and an increased likelihood of developing diabetes in later life. We have therefore studied seven women with gestational diabetes and five control women both during the third trimester of pregnancy and again 2–3 months post-partum, using the minimal model analysis of the frequently sampled labelled ([6, 6-2H2]-glucose) intravenous glucose tolerance test. Glucose tolerance (glucose Kd) was significantly reduced in the women with gestational diabetes compared with the normal pregnant women both in pregnancy (1.16 ± 0.11 vs 1.78 ± 0.23 %/min; p 〈 0.05) and post-partum (1.47 ± 0.22 vs 2.59 ± 0.43 %/min; p 〈 0.05) and increased significantly in the control women after delivery (p 〈 0.05). Glucose effectiveness was not significantly different between the women with gestational diabetes and the control group either during or after pregnancy. Insulin sensitivity was significantly lower during pregnancy than after delivery in the women with gestational diabetes (p 〈 0.05). There was no significant difference in basal insulin secretion in the two groups during pregnancy or post-partum. However, during pregnancy the control subjects significantly increased (p 〈 0.001) their insulin secretion over a period of 20 min in response to an intravenous glucose tolerance test (96.2 ± 42.7 pmol/kg) compared with post-partum values (58.3 ± 25.2 pmol/kg) while in the women with gestational diabetes insulin secretion was similar in pregnancy (65.5 ± 9.3 pmol/kg) and after delivery (57.7 ± 15.7 pmol/kg). These data suggest that the glucose intolerance in gestational diabetes compared to normal pregnancy is due to reduced insulin sensitivity and an impaired ability in gestational diabetes to increase insulin secretion in response to glucose. [Diabetologia (1996) 39: 976–983]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403918
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Demonstration of a relatively hepatoselective effect of covalent insulin dimers on glucose metabolism in dogs (1995)
    Springer
    Diabetologia 38 (1995), S. 1007-1013 
    Details
    ISSN: 1432-0428
    Keywords: Key words Insulin ; insulin analogues ; glucose metabolism ; euglycaemic clamp ; insulin action ; hepatoselectivity ; glucose production.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin analogues with relatively greater effect on hepatic glucose production than peripheral glucose disposal could offer a more physiological approach to the treatment of diabetes mellitus. The fact that proinsulin exhibits this property to a minor degree may suggest that analogues with increased molecular size may be less able than insulin to obtain access to peripheral receptor sites. Covalent insulin dimers have previously been shown to possess lower hypoglycaemic potencies than predicted by their in vivo receptor binding affinities. Reduced rates of diffusion to peripheral target tissues might be an explanation for the lower in vivo potency compared to insulin. To test the relative hepatic and peripheral effects of covalent insulin dimers, glucose clamp procedures with D-[3-3H]glucose tracer infusions were used in anaesthetised greyhounds to establish dose-response curves for rates of hepatic glucose production and glucose disposal with insulin, NαB1, NαB′ 1,-suberoyl-insulin dimer, and NɛB29, NɛB′ 29,-suberoyl-insulin dimer. With NαB1, NαB′ 1,-suberoyl-insulin dimer molar potencies relative to insulin were 68 %, (34–133) (mean and 95 % fiducial limits), for inhibition of hepatic glucose production and 14.7 %, (10.3–20.9) for glucose disposal. With NɛB29,NɛB′ 29,-suberoyl-insulin dimer potencies were 75 %, (31–184) and 2.5 %, (1.5–4.3), for inhibition of hepatic glucose production and for glucose disposal, respectively. The demonstration that both dimers exhibit a significantly greater effect on glucose production than on glucose disposal supports the suggestion that analogues with increased molecular size may exhibit reduced ability to gain access to peripheral target cells. [Diabetologia (1995) 38: 1007–1013]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402169
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Effect of recombinant human growth hormone treatment on insulin-like growth factor (IGF-I) levels in insulin-dependent diabetic patients (1995)
    Springer
    Acta diabetologica 32 (1995), S. 131-134 
    Details
    ISSN: 1432-5233
    Keywords: Type I diabetes mellitus ; Human recombinant growth hormone ; Insulin-like growth factor I ; Residual beta-cell activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Basal and recombinant human growth hormone (rhGH)-stimulated insulin-like growth factor (IGF-I) levels were studied in 19 insulin-dependent diabetic patients and 4 healthy subjects. Diabetic patients were divided according to glucagon test result into CpN (10 patients without residual beta cell activity) and CpP (9 patients with preserved beta-cell activity) groups, and according to age into three groups (A=21–30 years; B=31–40 years; C=41–50 years). All control subjects belonged to group B. Blood glucose and growth hormone were measured at hourly intervals and IGF-I every 6 h during 24 h before and after 7 days treatment with 4 IU of rhGH given subcutaneously at 8 p.m. The age-related decrease in basal IGF-I levels was evident in both CpN and CpP groups of diabetic patients. IGF-I net increase with rhGH treatment was variable and insignificant in comparison with basal value without age-related differences in CpN diabetics. Progressively larger age-related increases in IGF-I concentrations were observed in CpP diabetic patients. This study indicates impairment of hepatic IGF-I generation capacity in diabetic patients without residual beta-cell activity and the importance of simultaneous actions of portal insulin and GH on hepatic IGF-I production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00569572
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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