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The science of biotechnology
Published in Ronald P. Evens, Biotechnology, 2020
Sites of molecular alterations of insulin are identified in Figure 5.1 by a dotted circle around the specific amino acids (five such sites of change), which will be elucidated further below. The peptide sequence of insulin has been altered to create seven different new molecules with varied onsets and/or durations of activity in their glucose mechanism of action (e.g., aspart form, degludec, detemir, glargine, glulisine, glycine, lispro molecules). Insulin aspart has the B28 amino acid changed from proline to asparagine and has a rapid onset of action. The degludec form and the detemir form of insulin have the B30 threonine amino acid replaced with a carbon fatty acid chain (C-16 and C-14, respectively), imparting a long duration of action. The insulin glulisine molecule replaces two amino acids, B3 asparagine to lysine and B29 lysine to glutamine, causing a more rapid onset and shorter duration for its glucose actions. The insulin glargine form has one amino acid change at A21 from asparagine to glycine and two added arginine species to the carboxyl end of the B-chain, imparting a long action to the molecule. Insulin lispro molecule also possesses two amino acid changes, B28 proline to lysine and B29 lysine to proline, resulting in sustained activity.
Pharmacologic treatment of gestational diabetes mellitus: When to start and what agent to use
Published in Moshe Hod, Lois G. Jovanovic, Gian Carlo Di Renzo, Alberto de Leiva, Oded Langer, Textbook of Diabetes and Pregnancy, 2018
Celeste P. Durnwald, Mark B. Landon
The RAIA include insulin lispro, insulin aspart, and insulin glulisine. Of the rapid-acting analogues, insulin lispro is the most studied in pregnancy. A limited number of studies have also evaluated insulin aspart use in pregnancy, and no clinical studies to date have been published on insulin glulisine in pregnancy. Due to the similar pharmacologic action, the clinical experience related to transplacental passage, glycemic efficacy, and perinatal outcomes would not likely to be different based on the specific rapid-acting analogue used to treat women with GDM.
Pathophysiology and Clinical Management of Diabetes and Prediabetes
Published in Jeffrey I. Mechanick, Elise M. Brett, Nutritional Strategies for the Diabetic & Prediabetic Patient, 2006
Elliot J. Rayfield, Marilyn V. Valentine
RHI is structurally identical to human insulin and is synthesized by E. coli bacteria. It consists of zinc insulin crystals dissolved in clear fluid. Insulin lispro is a rapid-acting insulin analog in which the amino acids at positions 28 and 29 on the human insulin B-chain are reversed. Insulin aspart is another rapid-acting insulin analog with a substitution of aspartic acid for proline in position 28 on the B-chain. Insulin glulisine is the newest rapid-acting analog in which the aspargine at position 3 on the B-chain is replaced by lysine and the lysine at position 29 on the B-chain is replaced by glutamic acid. These amino acid changes result in a reduced propensity for insulin molecules to self-associate (form dimers and hexamers) giving them a more rapid onset and shorter duration of action than RHI. These insulins are used to cover carbohydrates at mealtimes, to correct an elevated glucose, and in insulin pumps.
Long-term stability of insulin glulisine loaded nanoparticles formulated using an amphiphilic cyclodextrin and designed for intestinal delivery
Published in Drug Development and Industrial Pharmacy, 2020
Elena Presas, Eric Sultan, Valeria Gervasi, Abina M. Crean, Ulrich Werner, Didier Bazile, Caitriona M. O’Driscoll
Animal experimental procedures were performed in compliance with German Animal Protection law under license FH/Anz. 1022 at Sanofi (Frankfurt, Germany). Healthy male Sprague-Dawley rats weighing 260–300 g were randomly assigned to the different groups. Animals were housed under controlled conditions of temperature and humidity with a 12:12 h light/dark cycle. The induction of anesthesia was performed using pentobarbital with an intraperitoneal injection dose of 65 mg/1000 g. Once under anesthesia, animals were maintained with a dose of 20 mg/1000 g/h utilizing an intraperitoneal injection. Rats were euthanized at the end of the experiments by overdosing with 0.5 mL pentobarbital intra-arterial. The in vivo studies were undertaken using an established in situ instillation method [18]. The intra-intestinal administration (single injection of 200 µL) of insulin glulisine NPs (75 IU/kg) and NaCl 0.9% (negative control group) was performed in situ after a midline laparotomy using a chronical implanted catheter (ID: 0.63 mm, OD: 1.02 mm). As a positive control, insulin glulisine was injected subcutaneously (1 IU/kg).
Strategies for implementing effective mealtime insulin therapy in type 2 diabetes
Published in Current Medical Research and Opinion, 2018
Mark Peyrot, Timothy S. Bailey, Belinda P. Childs, Gérard Reach
Mealtime insulin can be introduced for all three meals in a single step or in a step-wise process, starting with the meal with the highest glycemic excursion (basal-plus)62. However, various national and international medical society guidelines recommend a step-wise approach, suggesting the introduction of a basal-plus regimen (i.e. adding a single daily injection of rapid-acting insulin analog before the largest meal; either 4 units, 0.1 units/kg, or 10% of basal dose) before moving on to true basal-bolus therapy8,37,63. For individuals with T2D inadequately controlled on basal insulin, the addition of a single injection of insulin glulisine prior to the main meal significantly improved glucose control without undesired side-effects64,65. In the FULLStep study, step-wise mealtime insulin intensification has been shown to be as effective at controlling glucose levels as initial implementation of a full basal-bolus regimen of three daily mealtime injections, while significantly reducing hypoglycemia risks and improving patient satisfaction66. Titration follows based on target plasma glucose levels before meals (80–130 mg/dL [4.4–7.2 mmol/L]) or 1–2 h after that meal (<180 mg/dL [10.0 mmol/L])67.
Improving the treatment of patients with diabetes using insulin analogues: current findings and future directions
Published in Expert Opinion on Drug Safety, 2021
Eveline Lefever, Joke Vliebergh, Chantal Mathieu
Because of lack of data on the use of insulin glulisine during pregnancy, its use cannot be recommended during pregnancy. In contrast, insulin aspart and lispro are safe during pregnancy and some data suggest that these insulins may improve postprandial glycemic control in patients with T1DM. However, switching human insulin to insulin aspart/lispro in women with good glycemic control is not obligate because of lack of data demonstrating improved fetal outcomes, especially in women with T2DM and GDM where the evidence of benefit is even lower [113]. Faster-acting insulin aspart and ultra-rapid-acting insulin lispro, which formulations are only slightly adapted formulations of insulin aspart and insulin lispro, respectively, are deemed safe in pregnancy [106,114].