A Brief Atlas of Insulin

Abstract

Insulin is an essential factor for mammalian organisms: a regulator of glucose metabolism and other key signaling pathways. Insulin is also a multifunctional hormone whose absence can cause many diseases. Recombinant insulin is widely used in the treatment of diabetes. Understanding insulin, biosimilars and biobetters from a holistic perspective will help pharmacologically user-friendly molecules design and develop personalized medicine-oriented therapeutic strategies for diabetes. Additionally, it helps to understand the underlying mechanism of other insulin-dependent metabolic disorders. The purpose of this atlas is to review insulin from a biotechnological, basic science, and clinical perspective; explain nearly all insulin-related disorders and their underlying molecular mechanisms; explore exogenous/recombinant production strategies of patented and research-level insulin/analogs; and highlight their mechanism of action from a structural perspective. Combined with computational analysis, comparisons of insulin and analogs also provide novel information about the structural dynamics of insulin.

Comparative Study of High-resolution LysB29(Nε-myristoyl) des(B30) Insulin Structures Display Novel Dynamic Causal Interrelations in Monomeric-Dimeric Motions

“…Even though lipid modification of the proteins occurs routinely in nature, engineering strategies assist in understanding novel possibilities in oligomeric interactions, providing an enabling biotechnological tool for practical applications in drug therapy [11]. While numerous insulin structures are studied in dimer form, the presence of the fatty acid chain in the insulin paves the way to inspect the insulin in two-dimer form [7,9,10]. This provides the understanding of the dynamic profile of the molecule from an oligomeric perspective.…”

“…The efficiency, efficacy and simplicity of insulin analogs can facilitate the patient's transition to insulin therapy [6]. Moreover, studies have revealed insulin therapy's benefits, including the use of insulin analogs that offer various advantages over human insulin [6,7] Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content.…”

“…Insulin is produced by pancreatic β-cells as a monomer and stored in a hexameric form. The hexameric form is generated by three insulin dimers aggregating around two central zinc cations [7]. Various insulin analogs exist in the market which have been genetically engineered and formulations characterized by residual substitutions over the recombinant DNA technology [9].…”

Comparative Study of High-resolution LysB29(Nε-myristoyl) des(B30) Insulin Structures Display Novel Dynamic Causal Interrelations in Monomeric-Dimeric Motions

“…The efficiency, efficacy and simplicity of insulin analogs can facilitate the patient's transition to insulin therapy [6]. Moreover, studies have revealed insulin therapy's benefits, including the use of insulin analogs that offer various advantages over human insulin [6,7] (Supplementary Fig. 1).…”

“…The efficiency, efficacy and simplicity of insulin analogs can facilitate the patient’s transition to insulin therapy [6]. Moreover, studies have revealed insulin therapy’s benefits, including the use of insulin analogs that offer various advantages over human insulin [6,7] (Supplementary Fig.1). Various insulin analogs provide advantages consisting of greater convenience (Supplementary Fig.1), improved physiologic profile and a reduced risk of hypoglycemia [8].…”