Albumin binding and time action of acylated insulins in various species.

Novo Research Institute, Novo Nordisk A/S, Bagsvaerd, Denmark.
Journal of Pharmaceutical Sciences (Impact Factor: 3.01). 04/1996; 85(3):304-8. DOI: 10.1021/js950412j
Source: PubMed

ABSTRACT Insulins acylated with fatty acids at the epsilon-amino group of LysB29 constitute a new class of insulin analogs, which are prolonged-acting due to albumin binding. In the present study it is shown that the affinity of fatty acid acylated insulins for albumin varies considerably (> 50-fold) among species. The relative affinities of acylated insulin for albumin in human, pig, and rabbit serum are about 1:1:5:35. The several fold higher binding affinity in rabbit serum than in pig serum is reflected in a relatively more protracted effect after sc injection in rabbits than in pigs. Due to the similar binding affinities in pig serum and human serum, the pig model should provide a useful estimate of the degree of protraction of acylated insulin in humans. The results emphasize that species differences in ligand binding can be of major importance in the preclinical evaluation of highly albumin bound drugs.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A kind of novel biopolymer antioxidant (BSA/HOSalenM, M=Co, Mn, Zn) is prepared with conjugation, which increases the antioxidant activity of the bovine serum albumin (BSA). The conjugations have been characterized by IR spectra, UV-Vis spectra, Fluorescence spectra, Circular dichroism (CD) spectra and Native-PAGE. The BSA is used as a biopolymer scaffold, and the insoluble Salen Schiff-base metal complexes HOSalenM make axial coordination with the amino acid residues of the BSA. The structure of the BSA is unchanged when the binding rate of HOSalenCo is less than 10. The HOSalenCo conjugations show an excellent hydroxyl radical (·OH) scavenging activity, and the activity (EC50) of BSA/HOSalenCo(10) (BSA:HOSalenCo=1:10) is improved by two orders of magnitude compared with the BSA, while the activity of the BSA/HOSalenMn is weak and the BSA/HOSalenZn shows no scavenging activity.
    Chinese Science Bulletin 08/2013; · 1.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypoglycaemia remains an over-riding factor limiting optimal glycaemic control in type 1 diabetes. Severe hypoglycaemia is prevalent in almost half of those with long duration diabetes and is one of the most feared diabetes-related complications. In this review we present an overview of the increasing body of literature seeking to elucidate the underlying pathophysiology of severe hypoglycaemia and the limited evidence behind the strategies employed to prevent episodes. Drivers of severe hypoglycaemia including impaired counter-regulation, hypoglycaemia associated autonomic failure, psychosocial and behavioural factors, and neuroimaging correlates are discussed. Treatment strategies encompassing structured education, insulin analogue regimens, continuous subcutaneous insulin infusion pumps, continuous glucose sensing and beta-cell replacement therapies have been employed yet there is little RCT evidence demonstrating effectiveness of new technologies in reducing severe hypoglycaemia. Optimally designed interventional trials evaluating these existing technologies and using modern methods of teaching patients flexible insulin use within structured education programmes with the specific goal of preventing severe hypoglycaemia are required. Individuals at high risk need to be monitored with meticulous collection of data on awareness, frequency and severity of all hypoglycaemic episodes. This article is protected by copyright. All rights reserved.
    Diabetes/Metabolism Research and Reviews 11/2013; · 3.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Artículo de revisión Med Int Mex 2007;23(4):310-20 RESUMEN La mayor parte de los estudios ha demostrado que los pacientes con buen control glucémico disminuyen el padecimiento y la evolución de las retinopatías, nefropatías y neuropatías ocasionadas por la diabetes. La finalidad de los análogos de la insulina es controlar las concentraciones séricas de glucosa (hipoglucemia o hiperglucemia). Estos sustituyen ciertos aminoácidos en las cadenas a y b de la molécula de insulina que les confieren propiedades farmacodinámicas específicas, como: replicar el perfil más fisiológico de la insulina humana, mejorar el control glucémico y la calidad de vida de los pacientes. Esta revisión menciona las alternativas actuales relacionadas con los análogos de la insulina para el tratamiento de la diabetes mellitus. Palabras clave: diabetes mellitus, análogos de la insulina, farmacocinética, farmacodinámica. ABSTRACT Most of studies has demonstrated that patients with good glycemic control reduce retinopathies and its progression, and nephropathies and neuropathies due to diabetes. The aim of insulin analogues is to control hypoglycemic and hyperglycemic levels. These analogues replace certain aminoacids at a and b chains of insulin molecule, which gives it specific pharmacodynamic properties as: replication of most physiological profile of human insulin, and improving of glycemic control and patients quality of life. This revision deals with current alternatives related to insulin analogues on diabetes mellitus treatment.