AMT, an inducible nitric oxide synthase inhibitor, enhances islet engraftment.
We co-transplanted silica gel-entrapping 4H-1,3-Thiazin-2-amine,5,6-dihydro-6-methyl monohydrochloride (AMT) with islets to evaluate the effects of AMT on early graft dysfunction in a syngeneic mouse model. The mean diameter of AMT-embedding silica gel particles was 595 +/- 275 nm. The cumulative release of AMT was 29% at 1 hour and 45% at 72 hours. Sixteen streptozotocin-induced diabetic mice were separated into 3 groups. Group A received 50 islets (n = 4). Group B received 50 islets and blank silica gel (n = 6). Group C received 50 islets plus silica-gel containing 6.4 microg AMT (n = 6). Mice in group C required significantly less time for temporary posttransplantation hyperglycemia than those in groups A and B (A, 39 +/- 7 vs B, 40 +/- 5 vs C, 24 +/- 2 days; P < .05). The insulin contents of grafts retrieved at 13 weeks were 1.17 +/- 0.11 (n = 4), 1.01 +/- 0.16 (n = 6), and 1.68 +/- 0.30 microg (n = 6) for mice in groups A, B, and C, respectively. Pancreatic remnant insulin did not differ significantly between the 3 groups (A, 0.32 +/- 0.04 [n = 4] vs B, 0.29 +/- 0.06 [n = 6] vs C, 0.40 +/- 0.05 microg [n = 6]; P > .05). In vitro study revealed that 4 and 20 nmol/L of sol-gel-embedded AMT protected 87% and 96% RIN-m5F cells from 1 ng/mL interleukin-1beta-mediated destruction, respectively. Silica-gel-entrapped AMT protects islet graft from a nonspecific inflammatory destruction, which is partly mediated via interleukin-1beta.
Chen
Y-T
YT
Division of Endocrinology and Metabolism, Chang-Gung Memorial Hospital and Chang-Gung University, Tao-Yuan Hsien, Taiwan.
Fu
S-H
SH
Chen
J-P
JP
Hsu
B R-S
BR
D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D007328:Insulin / Q000097:blood; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009573:Nitrites / Q000097:blood; D053495:Osteopontin / Q000097:blood
D018076:DNA, Complementary; C507764:Il1rn protein, mouse; D007328:Insulin; D053590:Interleukin 1 Receptor Antagonist Protein; D009573:Nitrites; D053495:Osteopontin