title: Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist.
abstract: Islet transplantation is a feasible therapeutic alternative for metabolically labile patients with type 1 diabetes. The primary therapeutic target is stable glycemic control and prevention of complications associated with diabetes by reconstitution of endogenous insulin secretion. However, critical shortage of donor organs, gradual loss in graft function over time, and chronic need for immunosuppression limit the indication for islet transplantation to a small group of patients. Here we present a promising approach to address these limitations by utilization of a macrochamber specially engineered for islet transplantation. The s.c. implantable device allows for controlled and adequate oxygen supply and provides immunological protection of donor islets against the host immune system. The minimally invasive implantable chamber normalized blood glucose in streptozotocin-induced diabetic rodents for up to 3 mo. Sufficient graft function depended on oxygen supply. Pretreatment with the growth hormone-releasing hormone (GHRH) agonist, JI-36, significantly enhanced graft function by improving glucose tolerance and increasing β-cell insulin reserve in rats thereby allowing for a reduction of the islet mass required for metabolic control. As a result of hypervascularization of the tissue surrounding the device, no relevant delay in insulin response to glucose changes has been observed. Consequently, this system opens up a fundamental strategy for therapy of diabetes and may provide a promising avenue for future approaches to xenotransplantation.
authors.affiliation: Department of Medicine III,  University Hospital Carl Gustav Carus, 01307 Dresden,  Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ludwig
authors.forename: Avi
authors.initials: A
authors.lastname: Rotem
authors.forename: Janine
authors.initials: J
authors.lastname: Schmid
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Weir
authors.forename: Clark K
authors.initials: CK
authors.lastname: Colton
authors.forename: Mathias D
authors.initials: MD
authors.lastname: Brendel
authors.forename: Tova
authors.initials: T
authors.lastname: Neufeld
authors.forename: Norman L
authors.initials: NL
authors.lastname: Block
authors.forename: Karina
authors.initials: K
authors.lastname: Yavriyants
authors.forename: Anja
authors.initials: A
authors.lastname: Steffen
authors.forename: Stefan
authors.initials: S
authors.lastname: Ludwig
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichel
authors.forename: Dimitri
authors.initials: D
authors.lastname: Azarov
authors.forename: Baruch
authors.initials: B
authors.lastname: Zimermann
authors.forename: Shiri
authors.initials: S
authors.lastname: Maimon
authors.forename: Mariya
authors.initials: M
authors.lastname: Balyura
authors.forename: Tania
authors.initials: T
authors.lastname: Rozenshtein
authors.forename: Noa
authors.initials: N
authors.lastname: Shabtay
authors.forename: Pnina
authors.initials: P
authors.lastname: Vardi
authors.forename: Konstantin
authors.initials: K
authors.lastname: Bloch
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: Uriel
authors.initials: U
authors.lastname: Barkai
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D013007:Growth Hormone-Releasing Hormone / Q000819:agonists* / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016381:Islets of Langerhans Transplantation; D008422:Materials Testing; D010100:Oxygen / Q000378:metabolism*; D019397:Pancreas, Artificial; D011786:Quality Control; D051381:Rats
chemical_list: D013007:Growth Hormone-Releasing Hormone; D010100:Oxygen