Insulin analogues rapid acting

Rapid-acting insulin analogues (lispro, insulin aspart [Humalog, Novo log]) have been engineered to contain amino acid modifications that promote rapid entry into the circulation from subcutaneous tissue. They begin to exert their effects as early as 5 to 10 minutes after administration. Lispro insulin, the first insulin analogue to be approved in Europe and the United States, is produced by switching the positions of lysine-proline amino acid residues 28 and 29 of the carboxy terminus of the p-chain. Lispro insulin displays very similar actions to insulin and has a similar affinity for the insulin receptor, but it cannot form stable hexamers or dimers in subcutaneous tissue, which promotes its rapid uptake and absorption. 

Heinemann L, Weyer C, Rauhaus M, Heinrichs S, Heise T. Variability of the metabohc effect of soluble insulin and the rapid-acting insulin analogue insulin aspart. Diabetes Care 1998 21(ll) 1910-4. 

Becker R H, Frick A D, Burger F, et al. (2005). Insulin gulisine, a new rapid-acting insulin analogue, displays a rapid time-action profile in obese nondiabetic subjects. Exp. Clin. Endocrinol. Diabetes. 113 435-443. 

Heinemann, L., Heise, T., Jorgensen, L. N, and Starke, A. A. R., 1993b, Action profile of the rapid acting insulin analogue Hiunan insulin B28Asp, Diabetic Med. 10 535-539. 

Insulin Aspart is another rapid-acting insulin analogue produced from recombinant human insulin. In this case the B28, proline residue towards the terminus of the B chain is replaced by a negatively charged aspartate residue. The negative charge reduces the tendency of insulin to self-associate. 

Doping control analysis of intact rapid-acting insulin analogues in human urine by liquid chromatography-tandem mass spectrometry. Analytical Chemistry, 78,1897-1903. 

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