PHRM 211 Lecture Notes - Lecture 7: Diabetes Mellitus Type 1, Disulfide, Lipoatrophy
Document Summary
Med chem of diabetes drug (part 1) Intervening c-peptide is proteolytically removed active insulin hormone. Active insulin hormone 30-amino acid b chain + 21-amino acid a chain (linked through two disulfide bridges ) Prior to 1980s, bovine & porcine insulins were purified from animal pancreas used as mainstay of insulin substitution therapy. Allergic injection site reactions & lipoatrophy due to contaminants in preparation. Monocomponent or single peak (< 1 pmol/l protein impurity), semi-synthetic, human insulin : rigorously purified porcine insulin (ala b30 replaced with thr) Human insulin expressed recombinantly in bacteria or yeast replaced animal insulins. Insulin in granules of beta cells & standard insulins (nph) exist in hexameric form as a hexamer of heterodimers. A chain consists of two -helices orthogonally packed against -helix of b chain. B chain c-terminal forms antiparallel -sheet with adjacent b chain monomer additional stability to the hexamer.
