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  • 1
    ISSN: 1432-0428
    Keywords: Insulin analogues ; isolated fat cells ; biological potency ; lipogenesis ; inhibition of lipolysis ; combined biological action ; potentiation ; antagonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This paper presents a survey of the biological potencies of a variety of naturally-occurring and semi-synthetic insulin analogues and a study of the joint biological action of some of these materials with native insulin. Biological activity was tested on isolated rat fat cells using lipogenesis from glucose as the metabolic index. A brief comparison using inhibition of fat cell lipolysis was included. The results indicated: 1. Analogue potencies varied considerably (0.4–100% insulin activity). Values obtained were mainly confirmatory but included two further B1-modified materials and a tricarbamylated insulin. The results supported previous indications on the relative roles of the A1, B1, and B29 residues of insulin for hormone activity. 2. Analogue bioactivities, whether assessed by stimulation of lipogenesis or inhibition of lipolysis, were similar for the four materials tested in both systems. The response of fat cells with respect to both metabolic indices occurred over a comparable range of insulin concentrations, with half maximal effects at 30–35 pmol 1−1 insulin. 3. The presence of modified insulins appeared to alter the biological action of native insulinin vitro. Small effects of both potentiation and antagonism were identified.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Insulin structure-function ; chemically modified insulin ; proinsulin ; bioactivity of insulin analogues
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Beef insulin, pork proinsulin and four derivatives of beef insulin modified at the A1-B29 site on the molecular surface have been studied. Three derivatives had a synthetic crosslink between the A and B chains. Previous studies with these materials [2, 3 and 5] had demonstrated in vivo bioactivities which were much higher than those displayed in vitro. This paper reports experiments which explain this discrepancy. The analogues were administered at equimolar rates to anaesthetised greyhounds by a priming-dose constant infusion technique and the plasma concentrations achieved were estimated by radioimmunoassay. Proinsulin and the modified insulins were metabolised more slowly than insulin. Biopotency values, which related fall in plasma glucose concentration to the total administered dose of analogue, agreed broadly with published results of conventional in vivo bioassays. On the other hand, calculation of potency in relation to the serum concentration of analogue actually achieved, yielded results which agreed more closely with in vitro assay data. We conclude that for these analogues, reported discrepancies between in vitro and in vivo biopotencies can be largely explained by the different rates at which these materials are metabolised.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 17 (1979), S. 331-331 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Iodoinsulin ; insulin metabolism ; insulin analogues ; biological activity ; tracer insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin, specifically substituted at the PheB1 position with 3,5-diiodotyrosine, has been tested in several biological and immunological systems. Immunoreactivity was assessed using antisera specific for different parts of the insulin molecule. Biological activity in vitro was estimated on isolated rat fat cells. In vivo bioactivity (hypoglycaemia) and metabolism (metabolic and urinary clearance rates, half-life, apparent distribution space) were measured by infusion of the material into greyhounds. The results indicated that this B1-labelled insulin preparation was biologically fully active and, unlike randomly labelled preparations of iodoinsulin, was metabolised with kinetics indistinguishable from those of the unlabelled hormone. We suggest that this material is a valid tracer for insulin, fulfilling the criteria of high specific activity and biological identity to the native hormone.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    ISSN: 1432-0428
    Keywords: Chronic (maturity onset) diabetes mellitus ; glucose tolerance ; insulin and growth hormone secretion ; intermediary metabolites ; lipids ; diet treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty-five freshly presenting, diabetic patients received 5 hour, 100 g oral glucose tolerance tests when first seen and after a period of carbohydrate and energy restriction. After treatment, the significant improvement in glucose tolerance was accompanied by increased insulin secretion and lower concentrations of blood ketone bodies, lactate, glycerol, FFA, triglycerides, cholesterol and pre-beta lipoprotein. There were no significant changes in serum growth hormone or blood pyruvate concentrations. Improvement in glucose tolerance was greater in patients who were obese (〉115% of desirable body weight for height) on presentation and was related to the improvement in insulin secretion and the diminished lipolysis. An hypothesis to explain the changes in insulin secretion is proposed. Eleven out of the 35 patients showed sufficient improvement in glucose tolerance to require no treatment other than diet.
    Type of Medium: Electronic Resource
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  • 7
    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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  • 8
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 282 (1979), S. 11-12 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] THE German Wool Research Institute houses some of the foremost peptide chemists in the world who sharpen their teeth on insulin as a simple chemical model for the more complicated molecules that will be keeping us warm in the months to come. At the Institute two young students, Peter Thamm and ...
    Type of Medium: Electronic Resource
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