Proteomic Changes to the Updated Discovery of Engineered Insulin and Its Analogs: Pros and Cons

Abstract

The destruction of β-cells of the pancreas leads to either insulin shortage or the complete absence of insulin, which in turn causes diabetes Mellitus. For treating diabetes, many trials have been conducted since the 19th century until now. In ancient times, insulin from an animal's extract was taken to treat human beings. However, this resulted in some serious allergic reactions. Therefore, scientists and researchers have tried their best to find alternative ways for managing diabetes with progressive advancements in biotechnology. However, a lot of research trials have been conducted, and they discovered more progressed strategies and approaches to treat type I and II diabetes with satisfaction. Still, investigators are finding more appropriate ways to treat diabetes accurately. They formulated insulin analogs that mimic the naturally produced human insulin through recombinant DNA technology and devised many methods for appropriate delivery of insulin. This review will address the following questions: What is insulin preparation? How were these devised and what are the impacts (both positive and negative) of such insulin analogs against TIDM (type-I diabetes mellitus) and TIIDM (type-II diabetes mellitus)? This review article will also demonstrate approaches for the delivery of insulin analogs into the human body and some future directions for further improvement of insulin treatment.

Keywords: diabetes mellitus; hemoglobin A1C; hypoglycemia; insulin; insulin analogs.

Figure 1

A schematic block-diagram reveals how treatment against diabetes through insulin is improved over time from 1920s up to now. With the introduction of new technologies in the field of biotechnology, how different insulin analogs were discovered and bring improvements in the remediation against diabetes either TIDM or TIIDM.

Figure 2

Shows the proinsulin structure that is an inactive form of insulin (A-chain, B-chain, and C-peptide). Convertases I and II remove C-peptide by cleavage at two sites are shown by red circles, converting this inactive insulin to active human insulin.

Figure 3

Reveals that changes in human insulin produce insulin Lispro and insulin aspart. In case of Lispro, lys and pro amino-acid residues at position 29 and 28 of the B-chain, respectively, of human insulin interchange (pro at 29 and lys at 28 site) to form insulin lispro. In aspart insulin, aspart residue (shown as purple circle) is added to site-28 of B-chain instead of proline (at 28-site) that was originally present in human insulin.

Figure 4

In Glulisine analog, replacement occurs at two sites of the B-chain after the modification of human insulin. At carboxy-terminal, glulisine residue substituted lys residue at position 29, while at amino-terminal, lysine amino acid substituted Asn (shown by sky-colored rectangles).

Figure 5

Manifests the production of insulin glargine from human insulin by amino-acids replacement at both A and B-chain. At A-chain, in the carboxy-terminal, Gly residue replaced the Asn residue at 21-site shown by an arrowhead. While at B-chain, two additional Arg amino acids are added.

Figure 6

Reveals the formulations of detemir by the addition of some additional structures such as myristic acid is added to lys-29 to human insulin.

Figure 7

Reveals the formulations of Degludec insulin analog by the addition of some additional structures such as hex-decanedioic acid through Glu-linker is added to lys-29 of the B-chain of human insulin.