Treating type 1 diabetes remains a challenge even with the available advanced treatment modalities till now. Structural research of biomolecules provides evidence of various beneficial biological processes through the structural reorganization of biomolecules. A recent study from Indiana University published in ‘Proceedings of the National Academy of Science’ shows that ligand-induced structural modification of insulin provides better treatment for type 1 diabetes.

      The researchers focus on a feature already built into the shape of insulin– a protective 'hinge' that allows the protein to function when open, keeping it otherwise stable while closed by the insertion of an artificial ligand-dependent switch into the insulin molecule. The team used fructose to modify insulin so that it gets activated only in the presence of a certain amount of sugar. This scheme exploited a diol sensor (meta-fluoro-phenylboronic acid at GlyA1) and internal diol (3,4-dihydroxybenzoate at LysB28). The sensor recognizes monosaccharides (fructose > glucose).

      According to the researchers, the results provide proof of principle for the design of mechanism-based metabolite-responsive insulin. The replacement of the present fructose sensor by an analogous glucose sensor may enable the translational development of a “smart” insulin analogue to mitigate hypoglycemic risk in diabetes therapy.

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