title: Reduction of diffusion barriers in isolated rat islets improves survival, but not insulin secretion or transplantation outcome.
abstract: For people with type 1 diabetes and severe hypoglycemic unawareness, islet transplants offer hope for improving the quality of life. However, islet cell death occurs quickly during or after transplantation, requiring large quantities of islets per transplant. The purpose of this study was to determine whether poor function demonstrated in large islets was a result of diffusion barriers and if removing those barriers could improve function and transplantation outcomes. Islets were isolated from male DA rats and measured for cell viability, islet survival, glucose diffusion and insulin secretion. Modeling of diffusion barriers was completed using dynamic partial differential equations for a sphere. Core cell death occurred in 100% of the large islets (diameter >150 µm), resulting in poor survival within 7 days after isolation. In contrast, small islets (diameter <100 µm) exhibited good survival rates in culture (91%). Glucose diffusion into islets was tracked with 2-NBDG; 4.2 µm/min in small islets and 2.8 µm/min in large islets. 2-NBDG never permeated to the core cells of islets larger than 150 µm diameter. Reducing the diffusion barrier in large islets improved their immediate and long-term viability in culture. However, reduction of the diffusion barrier in large islets failed to improve their inferior in vitro insulin secretion compared to small islets, and did not return glucose control to diabetic animals following transplantation. Thus, diffusion barriers lead to low viability and poor survival for large islets, but are not solely responsible for the inferior insulin secretion or poor transplantation outcomes of large versus small islets.
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: S Janette
authors.initials: SJ
authors.lastname: Williams
authors.forename: Han-Hung
authors.initials: HH
authors.lastname: Huang
authors.forename: Karen
authors.initials: K
authors.lastname: Kover
authors.forename: Wayne
authors.initials: W
authors.lastname: Moore
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
authors.forename: Milind
authors.initials: M
authors.lastname: Singh
authors.forename: Irina V
authors.initials: IV
authors.lastname: Smirnova
authors.forename: Ronal
authors.initials: R
authors.lastname: MacGregor
authors.forename: Lisa
authors.initials: L
authors.lastname: Stehno-Bittel
mesh_terms: D000818:Animals; D016923:Cell Death; D002470:Cell Survival; D004058:Diffusion; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D008297:Male; D008954:Models, Biological; D016062:Porosity; D051381:Rats; D013194:Staining and Labeling; D016896:Treatment Outcome
chemical_list: D007328:Insulin; D005947:Glucose