title: Novel culture technique involving an histone deacetylase inhibitor reduces the marginal islet mass to correct streptozotocin-induced diabetes.
abstract: Islet transplantation is limited by the difficulties in isolating the pancreatic islets from the cadaveric donor and maintaining them in culture. To increase islet viability and function after isolation, here we present a novel culture technique involving an histone deacetylase inhibitor  (HDACi) to rejuvenate the isolated islets. Pancreatic islets were isolated from Sprague-Dawley (SD) rats and one group (FIs; freshly isolated islets) was used after overnight culture and the other group (RIs; rejuvenated islet) was subjected to rejuvenation culture procedure, which is composed  of three discrete steps including degranulation, chromatin remodeling, and regranulation. FIs and RIs were compared with regard to intracellular insulin content, glucose-stimulated insulin secretion (GSIS) capacity, gene expression profile, viability and apoptosis rate under oxidative stresses,  and the engraftment efficacy in the xenogeneic islet transplantation models. RIs have been shown to have 1.9 ± 0.28- and 1.7 ± 0.31-fold greater intracellular insulin content and GSIS capacity, respectively, than FIs. HDACi increased overall histone acetylation levels, with inducing  increased expression of many genes including insulin 1, insulin 2, GLUT2, and Ogg1. This enhanced islet capacity resulted in more resistance against oxidative stresses and increase of the engraftment efficacy shown by reduction of twofold marginal mass of islets in xenogeneic transplantation  model. In conclusion, a novel rejuvenating culture technique using HDACi as chromatin remodeling agents improved the function and viability of the freshly isolated islets, contributing to the reduction of islet mass for the control of hyperglycemia in islet transplantation.
authors.affiliation: Korea Islet Transplantation Institute, Inc., Seoul, Korea.
authors.forename: Jun-Seop
authors.initials: JS
authors.lastname: Shin
authors.forename: Byoung-Hoon
authors.initials: BH
authors.lastname: Min
authors.forename: Jong-Yeon
authors.initials: JY
authors.lastname: Lim
authors.forename: Byoung-Keun
authors.initials: BK
authors.lastname: Kim
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Han
authors.forename: Kun-Ho
authors.initials: KH
authors.lastname: Yoon
authors.forename: Sang-Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D046508:Culture Techniques / Q000379:methods*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology; D042541:Intracellular Space / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012060:Rejuvenation
chemical_list: D056572:Histone Deacetylase Inhibitors; D007328:Insulin; D005947:Glucose