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  • Articles: DFG German National Licenses  (6)
  • insulin structure-function  (2)
  • minimal model  (2)
  • oxygen consumption  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 15 (1978), S. 29-32 
    ISSN: 1432-0428
    Keywords: Thyroxine ; triiodothyronine ; reverse T3 ; glucose utilization ; glucose metabolic clearance rate ; ketones ; oxygen consumption ; cortisol ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thyroid hormones have been measured in normal subjects and insulin-requiring diabetic patients before and after treatment. Plasma thyroxine (T4) and 3, 3′, 5-triiodothyronine (T3) concentrations were both low in diabetics, with T3 frequently in the hypothyroid range, while 3, 3′, 5′-triiodothyronine (rT3) concentrations were elevated. All three returned to normal following treatment. T3 concentration was directly related to glucose utilization and metabolic clearance rate; and inversely related to plasma ketone body concentration. Thyroid hormone abnormalities in diabetes may reflect the degree of insulin-secreting capacity.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Chemically-modified insulins ; insulin structure-function ; bioactivity and metabolism in vivo ; competitive antagonism ; hypoglycaemia ; non-esterified fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The biological properties of three covalently-linked insulin dimers were studied in greyhounds. Constant infusions showed that the plasma distribution kinetics were slower for the dimers than for insulin. The metabolic clearance rates of the three dimers (10.3±0.4, 8.8±0.5, 8.2±0.5 ml· min-1· kg-1; mean ± SEM) were significantly lower than that of insulin (19±0.8 ml · min-1 · kg-1), and their hypoglycaemic effects (11.2%, 3% and 0.3%) were markedly reduced compared with their lipogenic potencies in vitro (80%, 30% and 13%, respectively). A low dose infusion of insulin or an equipotent dose of one of the dimers significantly prolonged the effects of an insulin bolus on plasma glucose but not on non-esterified fatty acids. The apparent distribution space (106.4±11.9 ml/kg) and clearance rate (14.7±0.5 ml · min-1 · kg-1) of an insulin bolus were significantly reduced by one dimer (44.5±8.4 ml/ kg and 10.7±2.8ml·min-1·kg-1) but not by the equipotent insulin infusion (102.7±8.2ml/kg and 16.4±0.07ml· min-1 · kg-1). The apparent partial competitive antagonism of insulin by the dimers that has been reported in vitro can be observed in vivo, in that antagonism of insulin metabolism was directly demonstrated with one of the dimers.
    Type of Medium: Electronic Resource
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  • 3
    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
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  • 4
    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
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 20 (1981), S. 94-101 
    ISSN: 1432-0428
    Keywords: Chemically modified insulins ; gluconeogenesis ; glucose turnover ; insulin structure-function ; proinsulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A [14C]-glucose tracer infusion method was used to compare the effects of insulin infusion on glucose metabolism with the effects of infusion of three semisynthetic modified insulins and of proinsulin. Insulin produced hypoglycaemia in the anaesthetised dog by decreasing hepatic glucose production and increasing peripheral glucose utilisation. Compensatory antihypoglycaemic mechanisms eventually modified these responses. A1 B29-Diacetyl insulin exerted an hypoglycaemic effect entirely by stimulation of peripheral glucose uptake. A1-B29 crosslinked insulins and proinsulin produced hypoglycaemia almost entirely by decreasing hepatic glucose production and had little effect on tissue uptake. These observations suggest that insulin analogues may have actions in vivo that are qualitatively different from those of native insulin and suggest that certain analogues have a predominant action on the liver. This has important therapeutic implications concerning the development of semisynthetic insulins for clinical use.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Glucose ; free fatty acids ; oxygen consumption ; respiratory quotient ; insulin ; cortisol ; triiodothyronine ; thyroxine ; ketone bodies ; energy ; balance ; insulin-dependent diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Turnover rates of glucose and free fatty acids were measured, using3H-glucose and14C-1-palmitic acid as tracers, in insulin-requiring diabetic patients at presentation and after insulin treatment. Correlations were sought with rates of substrate oxidation, determined independently from respiratory exchange, and with plasma hormone concentrations. The rates of appearance of glucose and of free fatty acids were increased in the diabetics to 17.6 and 10.2 μmol min−1 kg−1 respectively. Both rates fell to normal (13.3 and 7.1 μmol min−1 kg−1) after insulin. In the untreated state there was an inverse relationship between the rates of utilisation of glucose and free fatty acids (r=0.61; p〈0.05). It is suggested that this relationship represents the impairment of peripheral glucose utilisation by free fatty acids and by ketone bodies in vivo, so far only demonstrated in vitro. The tracer calculated rates of glucose utilisation correlated well over a wide range with the respiratory quotient in untreated diabetics, while respiratory quotient was inversely related to free fatty acid turnover rates. In untreated diabetics plasma cortisol and 3,3′, 5′-triiodothyronine (rT3) were increased whereas thyroxine and 3,5,3′-triiodothyronine (T3) were decreased. 3,5,3′-Triiodothyronine concentration was closely related to the metabolic clearance rate of glucose (p〈0.05), while cortisol concentrations correlated with glucose production (p〈0.02) and blood ketone body concentration (p〈0.02). It is concluded that glucose overproduction is the major contributor to the hyperglycaemia of untreated diabetes.
    Type of Medium: Electronic Resource
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