Insulin kinetically controlled

Further commercial interest was found by the transpeptidation reaction of porcine insulin to human insulin, the latter only differing in the last amino acid of Ae B-chain (Ala-B30 to Thr-B30). This reaction proceeds under kinetic control with trypsin, carboxypeptidase Y or achromobacter lyticus protease I. ... 

More importantly, IDDM patients have a defective glucose counterregulation. As Bolli and Perriello (1990) pointed out, counter-regulatory mechanisms in IDMM, compared with controls, are intact only in the first months after onset of diabetes. Thereafter, impaired insulin kinetics (due to... 

Studies on glucose-induced polymer swelling have focussed on developing membranes that could serve in systems for controlled delivery of insulin to diabetics (3,4). It has been shown that hydrophobic methacrylate copolymers undergo a sharp swelling transition as the pH is decreased from 7 to 6 (3-7). However, the kinetics of the transition are too slow for the proposed application to glucose delivery. 

A sustained drug release is favourable for drugs with short elimination half-life. It can be controlled by hydration and diffusion mechanisms or ionic interactions between the drug and the polymeric carrier. In the case of diffusion control the stability of the carrier system is essential, as its disintegration leads to a burst release. Therefore, the cohesiveness of the polymer network plays a crucial role in order to control the release over several hours. Due to the formation of disulphide bonds within the network thiomers offer adequate cohesive stability. Almost zero-order release kinetics could be shown for insulin embedded in thiolated polycarbophil matrices (Clausen and Bernkop-Schnurch 2001). In the case of peptide and protein drugs release can be controlled via ionic interactions. An anionic or cationic polymer has to be chosen depending... 

In addition to needles and syo inges, alternative techniques for insulin administration have been developed, some availing themselves of the kinetics of insulin insulin pens (supplied preloaded or with replaceable cartridges), external infusions and implantable pumps. These latter are convenient for cm accurately controlled continuously functioning biofeedback system, but pose difficulties for routine replacement in insulin deficiency. Therefore sustained-release (depot) formulations are used to provide an approach reasonably near to natural function and compatible with the convenience of daily living. An even closer approach is provided by the development of (at present inevitably expensive) miniaturised infusion pumps which can be used by reliable patients. 

Polyacrylamide forms water-based gels at concentrations around 4%w/v, which exhibit pseudoplastic behavior. A PAAm ophthalmic gel containing pilocarpine was compared with other gel vehicles the ocular bioavailability for the PAAm gel was three times greater than that of the aqueous control solution. The kinetics of ibuprofen release for crosslinked PAAm gels was studied. A kinetic model was proposed for swelling induced loading of insulin into crosslinked PAAm gels. ... 

In summary, the studies reported In this review provide 2 Important demonstrations (1) that In vitro release kinetics of macromolecules such as inulln from ethylene-vinyl acetate copolymer matrices are Identical to their In vivo release kinetics, and (2) that zero-order release for macromolecules can be achieved for over 60 days using a hemisphere design. Further experimentation in these areas should provide Information that will be useful In the eventual design of controlled release systems for Insulin and other important bloactlve macromolecules. 

Insulin and the counterregulatory hormones exert two types of metabolic regulation (see Chapter 26). The first type of control occurs within minutes to hours of the hormone-receptor interaction and usually results from changes in the catalytic activity or kinetics of key preexisting enzymes, caused by phosphorylation or dephosphorylation of these enzymes. The second type of control involves regulation of the synthesis of key enzymes by mechanisms that stimulate or inhibit transcription and translation of mRNA. These processes are slow and require hours to days. 

Brown, L., Siemer, L., Munoz, C. and Langer, R., Controlled release of insulin from polymer matrices in vitro kinetics. Diabetes, 35, 684, 1986. 

This is the name given to the study of the kinetics of drug absorption, distribution, metabolism, and excretion, all of which are rate-controlled. The earliest studies, which were concerned with inhaled anaesthetics (Widmark, 1920 Dominguez, 1933), were not suited for general application. The fundamental equations were introduced by T. Teorell (1937) in his studies of insulin action. He provided simple kinetic formulae to monitor the concentration of... 

Cobelli, C., Toffolo, G., and Ferrannini, E. 1984b. A model of glucose kinetics and their control by insulin. 

Control of Plasma and Liver Triglyceride Kinetics by Carbohydrate Metabolism and Insulin Esko A. Nikkild... 

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