Compounds, compositions, methods, and uses for treating insulin resistance, type 2 diabetes and metabolic syndrome

Abstract

Novel insulin, insulin-fusion proteins and insulin homologs protein-small molecule drug conjugates, where conjugation takes place through the use of cleavable and non-cleavable linkers are disclosed. The small molecules chemically linked to the protein carrier are imported into the specific insulin-responsive target tissue or cell through receptor-mediated endocytosis and released from the carrier protein through enzymatic cleavage of the linker-drug moiety or through lysosomal degradation of the carrier protein. Free drug can then act to modify insulin receptor-triggered biochemical pathways that are altered in conditions of insulin-resistance. Drug will correct altered pathway allowing re-sensitization of receptor signaling. This will greatly aid in the resolution of pathologies either initiated at the onset of insulin resistance or exacerbated by it.