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Insulin, You're Confusing the Systems
Author(s) -
Bartolomei Barrett A,
Mergens Steven Ryland,
Love Ryan Ann,
Shipley Ashley Willow,
Martinez Sandra Ann
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb214
Subject(s) - insulin , insulin receptor , endocrinology , beta cell , receptor , medicine , diabetes mellitus , hormone , insulin resistance , chemistry , islet
Insulin is a protein (hormone) that changes conformation to engage its receptor. In 2015 it affected an estimated 1.6 million deaths due to high blood glucose, from diabetes. Inability for insulin to bind to its receptor ultimately leads to the overabundance of glucose. This overabundance then leads to mitochondrial stress in pancreatic beta cells causing unwanted beta cell apoptosis and dysfunction. One component of the insulin change is the decrease in insulin sensitivity in the bloodstream due to glucose overexposure. Insulin becomes resistant to hormonal stimulation suggesting a change in the C‐terminal B‐chain segment. This conformational change insulin undergoes exposes the side chains IleA2, ValA3, ValB12, PheB24, and PheB25 to allow insulin to bind to its receptor. A further understanding of how the native folding is preserved and the binding sites that are blocked are opened, can open opportunities for additional clinical mutations in the insulin family and provide a basis for new research and therapeutic drugs, possibly leading to a more regulated interaction between insulin and glucose. Support or Funding Information PDB : 4OGA Primary Citation : Protective hinge in insulin opens to enable its receptor engagement. Menting, J.G., Yang, Y., Chan, S.J., Phillips, N.B., Smith, B.J., Whittaker, J., Wickramasinghe, N.P., Whittaker, L.J., Pandyarajan, V., Wan, Z.L., Yadav, S.P., Carroll, J.M., Strokes, N., Roberts, C.T., Ismail‐Beigi, F., Milewski, W., Steiner, D.F., Chauhan, V.S., Ward, C.W., Weiss, M.A., Lawrence, M.C. (2014) Proc.Natl.Acad.Sci.USA 111: E3395–E3404 The El Capitan High School CBM MAPS Team used 3‐D modeling and printing technology to examine structure‐function relationships of insulin. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .