Intrinsic Fibrillation of Fast-Acting Insulin Analogs

BD Technologies, Durham, North Carolina 27709, USA.
Journal of diabetes science and technology 03/2012; 6(2):265-76. DOI: 10.1177/193229681200600209
Source: PubMed


Background: Aggregation of insulin into insoluble fibrils (fibrillation) may lead to complications for diabetes patients such as reduced insulin potency, occlusion of insulin delivery devices, or potentially increased immunological potential. Even after extensive investigation of fibril formation in regular human insulin, there are little published data about the intrinsic fibrillation of fast-acting analogs. This article investigates and compares the intrinsic fibrillation of three fast-acting insulin analogs—lispro, aspart, and glulisine—as a function of their primary protein structure and exclusive of the stabilizing excipients that are added to their respective commercial formulations.

Full-text preview

Available from:
  • [Show abstract] [Hide abstract]
    ABSTRACT: Insulin has been in use for nearly a century, but its real clinical worth has been utilized only in the last one and half decade after the landmark study on tight glycaemic control by van Den Berghe. Intravenous (i.v.) insulin is the mainstay of treatment for hyperglycaemia in many acute settings as well as in managing diabetic complications. However, i.v. insulin usage may be associated with numerous potential errors which may have unintended consequences. A thorough knowledge of various aspects associated with insulin injection techniques such as preparations of i.v. insulin, calculation of correct dosage, precautions while using insulin with various i.v. fluids, formulating strategies to minimize insulin adsorption to tubing surface, choosing appropriate insulin injection accessories and devices, can help in optimal control of hyperglycaemia with minimal errors. Improvisation of insulin injection techniques is often necessary in resource challenged settings to minimize the morbidity and mortality associated with uncontrolled hyperglycaemia.
    No preview · Article · May 2013 · Journal of the Pakistan Medical Association
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since the formation of amyloid structures from proteins was recognized in numerous diseases, many efforts have been devoted to the task of finding effective anti-amyloidogenic compounds. In a number of these investigations, the existence of "generic" compounds is implicitly acknowledged. Curcumin seems to be one of these compounds, possessing key structural components effective toward fibrillation prevention, and its anti-amyloidogenic property has been reported for a number of model and disease-related proteins such as lysozyme and alpha-synuclein. In this study, insulin amyloid formation has been shown to be effectively influenced by micromolar concentrations of curcumin. Under amyloidogenic conditions (pH 2.5 and 37 °C), the compound was observed to inhibit fibril formation of insulin in a dose-dependent manner. Moreover, addition of curcumin to the protein incubated under such conditions at different time points resulted in reduced amounts of final fibrils. Disaggregation of pre-formed fibrils was also observed upon addition of curcumin, as well as reduction in final fibril amounts after seeding. Overall, this compound appears to be able to interact with native, intermediate and fibrillar forms. Docking experiments suggest a potential interacting site with the B-chain of insulin, as well as the possibility for beta-sheet breaker activity.
    No preview · Article · Sep 2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: We review and summarize the literature on the safety and stability of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion (CSII) in patients with diabetes. Two predefined search strategies were systematically implemented to search Medline and the Cochrane Register of Clinical Trials for publications between 1996 and 2012. Twenty studies were included in the review: 13 in vitro studies and 7 clinical studies. In vitro studies investigated the effects of extreme CSII conditions (high temperature and mechanical agitation) on the risk of catheter occlusions and insulin stability factors, such as potency, purity, high molecular weight protein content, pH stability, and preservative content (m-cresol, phenol). Under these conditions, the overall stability of rapid-acting insulin analogs was similar for insulin lispro, insulin aspart, and insulin glulisine, although insulin glulisine showed greater susceptibility to insulin precipitation and catheter occlusions. A limited number of clinical trials were identified; this evidence-based information suggests that the rate of catheter occlusions in patients with type 1 diabetes using CSII treatment may vary depending on the rapid-acting analog used. Based on a limited amount of available data, the safety, stability, and performance of the three available rapid-acting insulin analogs available for use with CSII were similar. However, there is limited evidence suggesting that the risk of occlusion may vary with the insulin preparation under certain circumstances.
    No preview · Article · Dec 2013 · Journal of diabetes science and technology
Show more