title: Beneficial effect of pretreatment of islets with fibronectin on glucose tolerance after islet transplantation.
abstract: The scarcity of available islets is an obstacle for clinically successful islet transplantation. One solution might be to increase the efficacy of the limited islets. Isolated islets are exposed to a variety of cellular stressors, and disruption of the cell-matrix connections damages islets. We examined the effect of fibronectin, a major component of the extracellular matrix, on islet viability, mass and function, and also examined whether fibronectin-treated islets improved the results of islet transplantation. Islets cultured with fibronectin for 48 hours maintained higher cell viability (0.146 +/- 0.010 vs. 0.173 +/- 0.007 by MTT assay), and also had a greater insulin and DNA content (86.8 +/- 3.6 vs. 72.8 +/- 3.2 ng/islet and 35.2 +/- 1.4 vs. 30.0 +/- 1.5 ng/islet, respectively) than islets cultured without fibronectin (control). Absolute values of insulin secretion were higher in fibronectin-treated islets than in controls; however, the ratio of stimulated insulin secretion to basal secretion was not significantly different (206.9 +/- 23.3 vs. 191.7 +/- 20.2% when the insulin response to 16.7 mmol/l glucose was compared to that of 3.3 mmol/l glucose); the higher insulin secretion was thus mainly due to larger islet cell mass. The rats transplanted with fibronectin-treated islets had lower plasma glucose and higher plasma insulin levels within 2 weeks after transplantation, and had more favorable glucose tolerance 9 weeks after transplantation. These results indicate that cultivation with fibronectin might preserve islet cell viability, mass and insulin secretory function, which could improve glucose tolerance following islet transplantation.
authors.affiliation: Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. yoshiyuki,hamamoto@joslin.harvard.edu
authors.forename: Y
authors.initials: Y
authors.lastname: Hamamoto
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
authors.forename: A
authors.initials: A
authors.lastname: Inada
authors.forename: M
authors.initials: M
authors.lastname: Takehiro
authors.forename: K
authors.initials: K
authors.lastname: Nabe
authors.forename: D
authors.initials: D
authors.lastname: Shimono
authors.forename: M
authors.initials: M
authors.lastname: Kajikawa
authors.forename: J
authors.initials: J
authors.lastname: Fujita
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D005353:Fibronectins / Q000627:therapeutic use*; D005951:Glucose Tolerance Test; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D008297:Male; D011300:Preoperative Care; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D005353:Fibronectins; D007328:Insulin; D004247:DNA