Attenuation of primary nonfunction for syngeneic islet graft using sodium 4-phenylbutyrate.
Sodium 4-phenylbutyrate (4-SPB), an aromatic derivative of butyric acid, was examined to elucidate its effect on islet engraftment in a syngeneic transplantation model using C57BL/6 mice. Diabetic mice that received subrenal implantation of 150 islets on day 0 and oral administration of twice daily 4-SPB (500 mg/kg body weight) on days -2 through 28 displayed a significantly shorter duration of posttransplantation temporary hyperglycemia than diabetic mice that received islets in isotonic sodium chloride solution (NaCl), namely 16 +/- 2 (n = 12) vs 23 +/- 2 days (n = 7; P < .05). Four weeks after transplantation, the insulin content (IC) of grafts from mice treated with islets and 4-SPB was substantially higher than that of grafts from mice treated with islets and NaCl, namely 2.59 +/- 0.37 (n = 8) vs 1.36 +/- 0.36 mug (n = 13; P < .01). The IC of pancreatic remnants showed no significant difference between groups after 2 and 4 weeks of incubation. In vitro studies demonstrated that the net glucose-stimulated insulin secretion (GSIS) and the ratio of net GSIS to the IC of islets cultured with 4-SPB (1 mM) did not differ significantly from those cultured with NaCl. The lipopolysaccharide-stimulated secretions of IL-1beta, IL-10, and IFNgamma from peritoneal exudate monocytes were significantly reduced by co-incubation with 4-SPB (1 mM). In conclusion, our data suggest that daily administration of 4-SPB reduces primary nonfunction and enhances islet engraftment in a syngeneic mouse transplantation model.
Fu
S-H
SH
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang-Gung Memorial Hospital, Linkou Medical Center, Kueishan County, Taoyuan Hsien, Taiwan.
Chen
S-T
ST
Hsu
B R-S
BR
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D006943:Hyperglycemia / Q000517:prevention & control; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010654:Phenylbutyrates / Q000494:pharmacology*; D011183:Postoperative Complications / Q000517:prevention & control; D013370:Subrenal Capsule Assay; D014185:Transplantation, Isogeneic / Q000502:physiology*
D010654:Phenylbutyrates; C075773:4-phenylbutyric acid