Insulin complexes

The concentration of insulin present in soluble insulin preparations (i.e. fast-acting insulins), is much higher (approximately 1 x KT2 3 mol I ). At this concentration, the soluble insulin exists as a mixture of monomer, dimer, tetramer and zinc-insulin hexamer. These insulin complexes have to dissociate in order to be absorbed from the injection site into the blood, which slows down the onset of hormone action. 

In another qualitative study, EDX analysis was used to study the nature of the precipitate occasionally formed in Zn-insulin solutions [73]. Identification of the EDX peaks obtained for the crystalline precipitates enabled the deduction that the solid consisted of a Zn-insulin complex, and a rough analysis of the peak intensities indicated that the composition of the precipitate was comparable to that existing in the starting materials. The combination of the EDX technique with scanning electron microscopy enabled the analyses to be conducted on relatively few numbers of extremely small particles. 

Trace metals Zinc Red meats, shellfish, wholegrain cereals Involved in many metabolic reactions stabilisation of structure RNA, DNA and ribosomes Binding of some transcription factors to DNA Stabilisation of insulin complex in storage granules... 

Protamine zinc insulin insulin complexed to excess protamine in order to prolong its duration of action... 

Recently a CD-insulin complex was encapsulated in polymethacrylic acid-chi-tosan-polyether[polyethylene glycol (PEG)-propylene glycol] copolymer PMCP nanoparticles from the free-radical polymerization of methacrylic acid in the presence of chitosan and polyether in a medium free of solvents or surfactants. Particles had a size distribution of 500-800 nm. The HP-B-CD inclusion complex with insulin was encapsulated into the nanoparticles, resulting in a pH-dependent release profile as seen in Figure 2. The biological activity of insulin was demonstrated with enzyme-... 

FIGURE 2 pH-dependent release profile for insulin complexed to HP-B-CD and encapsulated in nanoparticles. (Reprinted from S. Sajeesh and C. P. Sharma, International Journal of Pharmaceutics, 325,147-154, 2006, Copyright 2006, with permission from Elsevier.)... 

Sajeesh, S., and Sharma, C. P. (2006), Cyclodextrin-insulin complex encapsulated poly-methacrylic acid based nanoparticles for oral insulin delivery, Int. J. Pharm., 325, 147-154. 

Kotake Y, Ueda T, Mori T, Murakami E, and Hattori M (1975) The physiological significance of the xanthurenic acid-insulin complex. Journal of Biochemistry (Tokyo) 77, 685-7. 

Figure 9.19 offers a diagrammatic representation of the events following s.c. administration of a soluble human insulin existing initially as a hexameric zinc-insulin complex. 

Protein Hormones. Glycosylated insulin has been prepared (D21) and its biologic function shown to be reduced by 20%. However, the life of protein hormones in vivo is short, and so that negligible in vivo glycosylation occurs. The use of glycosylated insulin complexed to con-canavalin A in a closed-loop insulin delivery system has been described (B27) it presented stability advantages over conventional insulins in these situations. 

B27. Brownlee, M., and Cerami, A., Glyc-osylated insulin complexed to concanavalin A Biochemical basis for a closed-loop insulin delivery system. Diabetes 32, 499-504... 

Lente insulin is U-100 insulin complexed with zinc. It is intermediate-acting. 

Insulin complexed with zinc and protamine. This form of insulin has a slower onset and long duration. 

The insulin complex must first be degraded, because free insulin is the active form. Thus, the protein-protein interactions and also the zinc complexes must be disrupted. Because these interactions take time to disrupt, there is a lag time before the free insulin is released, resulting in slower onset. Because the complexed form allows more insulin to be administered per dose, the duration is long, because free insulin is released constantly upon disruption of the protein/zinc interactions. 

Insulin 2, because this insulin has an intermediate onset and duration, consistent with disruption of a protein-insulin complex. 

Di Abietes different preparations of insulin contain some insulin complexed with protamine that is absorbed slowly after injection. Protamine is a protein preparation from rainbow trout sperm containing arginine-rich peptides that bind insulin. Which of the following provides the best explanation for complex formation between protamine and insulin ... 

Although [Cr(OH2)6] and [Cr(OH)(OH2)5] continue to be the main starting species for anation studies (Table 6.5), there is a growing interest in the use of other aqua ions, such as ci5-[Cr(big)2(OH2)2] " or [Cr(ox)2(OH2)2] . In view of the interest in the biochemical role of Cr(III) in the Glucose Tolerance Factor (GTF), several Cr(III) aqua ions have been reacted with insulin and the products characterized after purification by dialysis. The chymotrypsin catalyzed hydrolysis of these Cr(III)-insulin complexes has also been investigated. " ... 

Dendritic and Hyperbranched Architectures. The first example of a PLL dendrimer synthesis vras patented hy Denkewalter et The authors described a divergent stepwise synthetic route starting from N -bis(Boc)-L-lysine benzhydrylamide. The dendritic macromolecule with a PDI close to 1 was built through repetitive coupling with a Boc-protected lysine derivative activated with p-nitrophenyl ester, followed by deprotection. Furthermore, dendritic PLL macromolecules were functionalized on the surface with arginine end-groups for insulin complexation. ... 

Insulin antibodies have been separated by paper electrophoresis from the blood of insulin-treated patients. These antibodies act on insulin labeled with iodine 131, and a cross reaction occurs between the antibodies and insulin obtained from humans, pork, and beef. Insulin antibodies appear in the blood after bovine or foreign insulin administration. The amount of antibody is proportional to the amount of insulin injected. The antibody insulinic complex has little insulinlike activity. Insulin antibody develops in those patients who receive large doses of insulin, and it is therefore impossible to judge whether the insulin resistance results from antibody formation or from the appearance of agents with autoimmune activity. 

Whereas extensive purification has resulted in a very pure and homogeneous insulin product, the protamine used for retardation in NPH type preparations (see Section 2.2.1) is highly inhomogeneous as it contains four major components, which are present in approximately equal amounts. AU four components show close structural homology with one another, and consequently they generate nearly identical protamine-insulin complexes (Hoffinaneta/., 1990). 

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