The Function Of Insulin Or Rapid-Acting Insulin Analogs

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insulin or rapid-acting insulin analogs Preparations included with phenolic excipients serves two purposes: retaining solution sterility and stabilization of the insulin molecule in the hexameric form to avoid aggregation(35). These compounds are may cause problems since they are proved to be toxic and irritant, and are being investigated for their role as sensitizers and carcinogens (36).

Generally the human insulin monomers may assemble into insulin dimer and insulin hexamer which is more stable than that of dimeric form. Regarding the main function of insulin which is regulating the uptake of glucose, both insulin dimer and hexamer are inactive in biological environment. However they are much more stable from conformational viewpoint
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When phenolic preservatives were depleted insulin glulisine dissociated or broke down from a structure with higher molecular weight (hexamer) structures into a number of intermediate molecular weight one, usually between monomer and hexamer, whereas insulin aspart and insulin lispro separated into monomers and dimmers. The ultimate disintegration of Insulin lispro and aspart was due to the large extent of their dissociation when they were depleted of their excipients while insulin glulisine was dissociated to intermediate molecular weight molecules in the absence of the phenol and m-cresol (39).

In general they concluded that insulin degradation was inversely related to the concentration of phenol and m-cresol as phenolic preservatives.

Tissue response and inflammation (cytotoxic effect of insulin with and without excipients)

CD54, CD11b and CD14 are surface proteins considered as markers of inflammatory cell activation. Weber et al explored these markers to investigate whether the phenol and m-cresol could cause the inflammatory response. In order to study the potential inflammatory effect of phenolic preservatives of insulin they selected monocytic cell line THP-1. The mentioned cell lines were exposed to sub-toxic concentration of phenol and m-cresol as well as insulin analogues formulation for 24 hours. Since they found that insulin with
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