New Insights into the Turnover of Pancreatic Hormones Insulin and Amylin in Pancreatic Islets
Aleksandar JeremicDiti Chatterjee BhowmickSanghanutra Singh
摘要：Following glucose stimulation,the two major pancreatic hormones,amylin and insulin,are secreted from pancreatic *-cells to maintain glucose homeostasis.Following biosynthesis and proteolytic cleavage by pro-convertases 1-3,these two hormones are stored in secretory vesicles as mature 4-6 kD a polypeptides ready to be released by various secretagouges.Studies show that human amylin misfolds and aggregates in pancreatic-cells of diabetic patients leading to islet amyloid formation and type-2 diabetes mellitus（T2 DM）.Under normal physiological conditions,cellular proteolytic compartments and complexes,lysosomes and proteasomes,degrade misfolded proteins including these two pancreatic hormones thereby preventing islet cells from undergoing protein stress.Conversely,deregulated cellular proteolytic system triggers protein stress via accumulation of toxic amylin-derived oligomers and aggregates in the pancreas,which ultimately causes beta-cell death.Here,new findings concerning the role of proteasome complex in amylin’s and insulin’s biosynthesis and proteolytic processing in islet beta-cells,relevant to etiology of islet amyloidosis and T2 DM,will be presented and discussed.
BIT’s 6th World Congress of Endobolism-2017 & BIT’s 5th World Congress of Diabetes-2017（WCE & WCD-2017）
Prague, Czech Republic