Measurement of interstitial albumin in human skeletal muscle and adipose tissue by openflow microperfusion. The relationship between insulin bioactivity and structure in the NH2-terminal A-chain helix. Structural effects of protein lipidation as revealed by Lys B29-myristoyl, des(B30) insulin. Crystal structure of a prolonged-acting insulin with albumin-binding properties. A novel principle of protraction of potential use for basal insulin delivery. Receptor binding and tyrosine kinase activation by insulin analogues with extreme affinities studied in human hepatoma HepG2 cells. Albumin binding of acylated insulin (NN304) does not deter action to stimulate glucose uptake. Mode of transcapillary transport of insulin and insulin analog NN304 in dog hindlimb. Mechanism of protracted metabolic effects of fatty acid acylated insulin, NN304, in dogs: retention of NN304 by albumin. Pharmacokinetic and pharmacodynamic properties of long-acting insulin analogue NN304 in comparison to NPH insulin in humans. Time-action profile of the soluble, fatty acid acylated, long-acting insulin analogue NN304. Effect of fatty acids and selected drugs on the albumin binding of a long-acting, acylated insulin analogue. Soluble fatty acid insulins bind to albumin and show protracted action in pigs. Albumin binding of insulin acylated with fatty acids: characterization of the ligand-protein interaction and correlation between binding affinity and timing of the insulin effects in vivo. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Time-action profile of the long-acting insulin analogue insulin glargine (HOE901) in comparison with those of NPH insulin and placebo. Insulin analogues and their potential in the management of diabetes mellitus. Degree of protraction and crystallizability of insulins substituted in positions A17, B8, B13, B27 and B30. Soluble, prolonged-acting insulin derivatives. Soluble, prolonged-acting insulin derivatives, I: Degree of protraction and crystallizability of insulins substituted in positions A17, B8, B23, B27 and B30. Comparison with NPH insulin and the influence of different subcutaneous injection sites. Pharmacokinetics of 125I-labelled insulin glargine (HOE 901) in healthy men. A randomised open crossover trial in type 1 diabetic subjects on basal-bolus therapy. Comparison of the soluble basal insulin analog insulin detemir with NPH insulin. Insulin glargine: the first clinically useful extendedacting insulin in half a century? Exp. Physiological insulin replacement in type 1 diabetes mellitus. Insulin analogs with improved pharmacokinetic profiles. Monomeric insulins and their experimental and clinical implications. Subcutaneous absorption of insulin in insulindependent diabetic patients. Variation in insulin absorption and blood glucose concentrations. Monomeric insulins obtained by protein engineering and their medical implications. ![]() Sestoft Diffusion and polymerisation determine the insulin absorption from subcutaneous tissue in diabetic patients. Evidence from absorption studies of soluble human insulin and insulin analogues in humans. Subcutaneous insulin absorption explained by insulin's physicochemial properties. ![]() Some possible zinc-insulin interactions in the pancreatic B-cell. Insulin detemir provides a novel principle of protraction, enabling increased predictability of basal insulin. Some further retention of detemir occurs in the circulation where albumin binding causes buffering of insulin concentration. Dihexamerization and albumin binding of hexameric and dimeric detemir prolongs residence time at the injection depot. ![]() The protracted action of detemir is primarily achieved through slow absorption into blood. ![]() Intravenous kinetic studies showed that the clearance and volume of distribution decreased with increasing albumin binding affinity of different acylated insulin analogs.Ĭonclusions. Self-association of acylated insulin analogs with same albumin affinity in saline correlated with disappearance rate and addition of albumin to saline showed a combination of insulin detemir self association and albumin binding. Disappearance T 50% from the injection depot was 10.2 ± 1.2 h for insulin detemir and 2.0 ± 0.1 h for a monomeric acylated insulin analog. Size-exclusion chromatography was used to assess the self-association and albumin binding states of insulin detemir and analogs. The disappearance from an injected subcutaneous depot and elimination studies in plasma were carried out in pigs. A series of experiments were performed to elucidate the underlying mechanisms. Insulin detemir has been found in clinical trials to be absorbed with very low variability.
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