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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
    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
    BibTip Others were also interested in ...
    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: 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
  • 4
    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
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