Synthetic beta cells for fusion-mediated dynamic insulin secretion. Academic Article uri icon

abstract

  • Generating artificial pancreatic beta cells by using synthetic materials to mimic glucose-responsive insulin secretion in a robust manner holds promise for improving clinical outcomes in people with diabetes. Here, we describe the construction of artificial beta cells (ACs) with a multicompartmental 'vesicles-in-vesicle' superstructure equipped with a glucose-metabolism system and membrane-fusion machinery. Through a sequential cascade of glucose uptake, enzymatic oxidation and proton efflux, the ACs can effectively distinguish between high and normal glucose levels. Under hyperglycemic conditions, high glucose uptake and oxidation generate a low pH (<5.6), which then induces steric deshielding of peptides tethered to the insulin-loaded inner small liposomal vesicles. The peptides on the small vesicles then form coiled coils with the complementary peptides anchored on the inner surfaces of large vesicles, thus bringing the membranes of the inner and outer vesicles together and triggering their fusion and insulin 'exocytosis'.

published proceedings

  • Nat Chem Biol

altmetric score

  • 172.89

author list (cited authors)

  • Chen, Z., Wang, J., Sun, W., Archibong, E., Kahkoska, A. R., Zhang, X., ... Gu, Z.

citation count

  • 160

complete list of authors

  • Chen, Zhaowei||Wang, Jinqiang||Sun, Wujin||Archibong, Edikan||Kahkoska, Anna R||Zhang, Xudong||Lu, Yue||Ligler, Frances S||Buse, John B||Gu, Zhen

publication date

  • January 2018