Insulin stability

Proinsulin is proteolytically processed in the coated secretory granules, yielding mature insulin and a 34-amino acid connecting peptide (C peptide, Figure 11.1). The C peptide is further proteolytically modified by removal of a dipeptide from each of its ends. The secretory granules thus contain low levels of proinsulin, C peptide and proteases, in addition to insulin itself. The insulin is stored in the form of a characteristic zinc-insulin hexamer, consisting of six molecules of insulin stabilized by two zinc atoms. 

I. Amar-Yuli, D. Azulay, T. Mishrald, A. Aserin, N. Garti, The role of glyeerol and phosphatidylcholine in solubilizing and enhancing insulin stability in reverse hexagonal mesophases. J. Colloid Interf. Sci. 364, 379-387 (2011)... 

It should be made clear from the start that a direct effect of insulin on glucose phosphorylation has never been satisfactorily demonstrated in muscle or brain. (In 1946, Berger and his associates discovered that the addition of insulin stabilizes hexokinase activity. This was, however, an unspecific effect that could also be produced by many other proteins.) Consequently, all arguments in support of an effect of insulin on hexokinase in those tissues are indirect. Brief analysis of the following results shows that much of this work on the action of insulin on hexokinase needs confirmation. 

Silva, C. M., Ribeiro, A. J., Figneiredo, I. V., Gon9alves, A. R. and Veiga, F. (2006). Alginate microspheres prepared by internal gelation development and effect on insulin stability. International Journal of Pharmaceutics, 311,1-10. 

Type 2 diabetes adjunct to insulin therapy in the stabilization of certain cases of insulin-dependent diabetes (type 1)... 

Type 2 diabetes adjunct to metformin when adequate results are not achieved with either drug alone adjunct to insulin in stabilization of certain individuals with type 1 diabetes... 

Exposure to stress such as infection, fever, surgery, or trauma, may cause a toss of control of blood glucose levels in patients who have been stabilized with oral antidiabetic drugs. Should this occur, the health care provider may discontinue use of the oral drug and administer insulin. 

Insulin, a small protein of molecular mass 6000 daltons, is composed of two chains designated A and B. There are no reduced cysteine residues in insulin, but it contains three essential disulfide bonds two that crosslink the A and B chains, and one internal to the A chain to stabilize the overall tertiary stmcture. These disulfide bonds are cleaved in the presence of excess AuX4, leaving A and B chains that have cysteine residues that have become oxidized to sulfonic adds [119]. With smaller amounts of AuX4, a single disulfide bond will be attacked to form sulfinic acid [119]. The reaction is second order for AuCU while AuBr4 reacts too quickly for accurate monitoring. 

Patients with acute hyperkalemia usually require other therapies to manage hyperkalemia until dialysis can be initiated. Patients who present with cardiac abnormalities caused by hyperkalemia should receive calcium gluconate or chloride (1 g intravenously) to reverse the cardiac effects. Temporary measures can be employed to shift extracellular potassium into the intracellular compartment to stabilize cellular membrane effects of excessive serum potassium levels. Such measures include the use of regular insulin (5 to 10 units intravenously) and dextrose (5% to 50% intravenously), or nebulized albuterol (10 to 20 mg). Sodium bicarbonate should not be used to shift extracellular potassium intracellularly in patients with CKD unless severe metabolic acidosis (pH less than 7.2) is present. These measures will decrease serum potassium levels within 30 to 60 minutes after treatment, but potassium must still be removed from the body. Shifting potassium to the intracellular compartment, however, decreases potassium removal by dialysis. Often, multiple dialysis sessions are required to remove potassium that is redistributed from the intracellular space back into the serum. 

Somatostatin. Somatostatin is an endogenous peptide hormone involved in e.g. the control of the release of Somatomedin, Insulin and Pancreatin. Due to its biological role, Somatostatin has a very low biological stability. The half-life in the rabbit after intravenous administration has been determined to approximately 90 seconds in this investigation. After sc or im administration, the apparent half-life is somewhat longer, close to 10 minutes, probably due to the absorption of the peptide from the injection site into the systemic circulation. 

J. Brange, S. Havelund, and P. Hougaard, Chemical stability of insulin 2 Formation of higher molecular weight transformation products during storage of pharmaceutical preparations, Pharm. Res, 9, 727 (1992). 

The insulin-like growth factor I receptor is closely related to the insulin receptor. The RTK activity of the IGF-I receptor is regulated by intermolecular autophosphorylation at three sites within the activation loop. The crystal structure of the trisphosphorylated form of IGF-I RTK domain with an ATP analog and a specific peptide substrate showed that autophosphorylation stabilizes the activation loop in a conformation that facilitates catalysis. Furthermore, the structure revealed how... 

Akiyoshi K, Kobayashi S, Shichibe S et al (1998) Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs Complexation and stabilization of insulin. J Control Release 54 313-320... 

Safety is an important factor when determining the quality of any iontophoresis electrode. During transdermal iontophoretic delivery using metal electrodes, an applied DC current will induce pH changes on the electrode/skin interface [178], pH measurement is used to eliminate the possibility of unsafe pH changes (chemical bums). It has been reported that the pH shift caused by platinum electrodes has a significant influence on the permeation and stability of insulin [175],... 

Proteins may be stabilized by encapsulation in polyanhydride microspheres. Stability of proteins with respect to water-induced aggregation has been demonstrated to be a function of polymer hydrophobicity for insulin and bovine somatotropin as model proteins (Ron et al., 1993). Encapsulation and enzymatic activity of a variety of other proteins encapsulated in P(SA FAD) was studied by Tabata et al. (1993). 

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