Beneficial effect of pretreatment of islets with fibronectin on glucose tolerance after islet transplantation.
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.
Hamamoto
Y
Y
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. yoshiyuki,hamamoto@joslin.harvard.edu
Fujimoto
S
S
Inada
A
A
Takehiro
M
M
Nabe
K
K
Shimono
D
D
Kajikawa
M
M
Fujita
J
J
Yamada
Y
Y
Seino
Y
Y
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
D001786:Blood Glucose; D005353:Fibronectins; D007328:Insulin; D004247:DNA