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- W3174565467 abstract "For people with diabetes, maintaining blood glucose levels within the nondiabetic range is effective in delaying or even preventing long-term complications, but achieving near normoglycemia is still challenging for these patients. This is due to the fact that the current fast-acting insulin, Humalog, still has relatively slow absorption after subcutaneous injection which leads to delayed insulin response and sub-optimal control of glycemia. An even faster-acting insulin requires a monomeric insulin molecule. However, the region of the insulin molecule responsible for self-association is also responsible for insulin receptor binding. Therefore, despite millions of dollars invested, a truly monomeric, ultrafast-acting insulin remains to be invented. In this project, we take a bio-inspired approach to utilize a venom insulin as a potential candidate with ultrafast-acting properties. Recently, we and collaborators reported that a cone snail venom insulin, Con-Ins G1, is monomeric in nature due to its shortened B-chain. Furthermore, Con-Ins G1 is bioactive toward human insulin signaling, albeit with 20-fold reduction in potency. Learning from the structural insights, we performed a series of structure-activity relationship studies to identify the key mutations from Con-Ins G1 that lead to increased bioactivity. We have identified A8H, A9R, B10E, B20Y Des-octapeptide (B23–30) insulin “mini-Ins” as the shortest bioactive human insulin analog discovered to date. In vitro and in vivo experiments demonstrated equal biological potencies between native insulin, Humalog and mini-Ins. The discovery of mini-Ins demonstrates a promising therapeutic potential as a monomeric insulin. Support or Funding Information This work was supported by Utah Science Technology and Research Agency and the Margolis Foundation. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal." @default.
- W3174565467 created "2021-07-05" @default.
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- W3174565467 date "2018-04-01" @default.
- W3174565467 modified "2023-09-27" @default.
- W3174565467 title "Mini‐Ins: a Monomeric Human Insulin Inspired From Cone Snail Venom Peptides" @default.
- W3174565467 doi "https://doi.org/10.1096/fasebj.2018.32.1_supplement.798.16" @default.
- W3174565467 hasPublicationYear "2018" @default.
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