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Insulin: a small protein with a long journey

Protein & Cell 2010年第6期1卷 537-551页

作者： Qingxin Hua Department of Biochemistry Case Western Reserve UniversityClevelandOhio 44106-4935USA

Insulin is a hormone that is essential for regulating energy storage and glucose metabolism in the *** in liver,muscle,and fat tissues stimulates the cell to take up glucose from blood and store it as glycogen in liver and *** of insulin control causes diabetes mellitus(DM).Insulin is the unique medicine to treat some forms of *** population of diabetics has dramatically increased over the past two decades,due to high absorption of carbohydrates(or fats and proteins),lack of physical exercise,and development of new diagnostic *** present,the two largest developing countries(India and China)and the largest developed country(United States)represent the top three countries in terms of diabetic *** is a small protein,but contains almost all structural features typical of proteins:α-helix,β-sheet,β-turn,high order assembly,allosteric T→R-transition,and conformational changes in amyloidal *** than ten years’efforts on studying insulin disulfide intermediates by NMR have enabled us to decipher the whole picture of insulin folding coupled to disulfide pairing,especially at the initial stage that forms the nascent *** structural switches are also known to regulate insulin binding to receptors and progress has been made to identify the residues involved in ***,resolving the complex structure of insulin and its receptor remains a challenge in insulin ***,the accumulated knowledge of insulin structure has allowed us to specifically design a new ultra-stable and active single-chain insulin analog(SCI-57),and provides a novel way to design super-stable,fast-acting and cheaper insulin formulations for DM *** this long journey of insulin study will benefit basic research in proteins and in pharmaceutical therapy.

关键词： insulin diabetes receptor binding folding disulfide pairing NMR

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