OBJECTIVES: We investigated whether the recovery of cultured human islets is improved through the addition of a p38alpha-selective mitogen-activated protein kinase inhibitor, SD-282, to clinically used serum-free culture medium. METHODS: Immediately after isolation, islets were cultured for 24 hours in medium alone (control) or medium containing dimethyl sulfoxide, 0.1 microM SD-282, or 0.3 microM SD-282. Cytokine expression, apoptotic beta-cell percentage, and islet function were assessed postculture. RESULTS: Expression of p38 and phosphorylated p38 in islets increased during culture. Interleukin 6 mRNA expression in cultured islets, as well as IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor released into the medium, was significantly reduced by adding SD-282. The apoptotic beta-cell percentage was significantly lower in islets cultured with 0.1 microM SD-282, but not 0.3 microM, as compared with the control. Stimulation indices measured in vitro were higher but without significance (P = 0.06); the function of transplanted islets in diabetic NOD-scid mice was also better in 0.1-microM SD-282 group as compared with control. CONCLUSIONS: Better islet function was obtained by adding 0.1 microM SD-282 to the serum-free culture medium. This improvement was associated with suppression of cytokine production and prevention of beta-cell apoptosis. However, this beneficial effect was diminished at a higher concentration.
OBJECTIVES: We investigated whether the recovery of cultured human islets is improved through the addition of a p38alpha-selective mitogen-activated protein kinase inhibitor, SD-282, to clinically used serum-free culture medium. METHODS: Immediately after isolation, islets were cultured for 24 hours in medium alone (control) or medium containing dimethyl sulfoxide, 0.1 microM SD-282, or 0.3 microM SD-282. Cytokine expression, apoptotic beta-cell percentage, and islet function were assessed postculture. RESULTS: Expression of p38 and phosphorylated p38 in islets increased during culture. Interleukin 6 mRNA expression in cultured islets, as well as IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor released into the medium, was significantly reduced by adding SD-282. The apoptotic beta-cell percentage was significantly lower in islets cultured with 0.1 microM SD-282, but not 0.3 microM, as compared with the control. Stimulation indices measured in vitro were higher but without significance (P = 0.06); the function of transplanted islets in diabetic NOD-scid mice was also better in 0.1-microM SD-282 group as compared with control. CONCLUSIONS: Better islet function was obtained by adding 0.1 microM SD-282 to the serum-free culture medium. This improvement was associated with suppression of cytokine production and prevention of beta-cell apoptosis. However, this beneficial effect was diminished at a higher concentration.
Authors: S Hashimoto; Y Gon; K Matsumoto; S Maruoka; I Takeshita; S Hayashi; Y Asai; I Jibiki; T Machino; T Horie Journal: J Pharmacol Exp Ther Date: 2000-05 Impact factor: 4.030
Authors: Rita Bottino; A N Balamurugan; Hubert Tse; C Thirunavukkarasu; Xinhui Ge; Jennifer Profozich; Martha Milton; Audra Ziegenfuss; Massimo Trucco; Jon D Piganelli Journal: Diabetes Date: 2004-10 Impact factor: 9.461
Authors: Nina L Tsakadze; Utpal Sen; Zhendong Zhao; Srinivas D Sithu; William R English; Stanley E D'Souza Journal: Am J Physiol Cell Physiol Date: 2004-02-18 Impact factor: 4.249
Authors: Juan L Contreras; Christopher Eckstein; Cheryl A Smyth; Marty T Sellers; Mario Vilatoba; Guadalupe Bilbao; Firoz G Rahemtulla; Carlton J Young; J Anthony Thompson; Irshad H Chaudry; Devin E Eckhoff Journal: Diabetes Date: 2003-12 Impact factor: 9.461
Authors: K Omori; M Mitsuhashi; K Ishiyama; I Nair; J Rawson; I Todorov; F Kandeel; Y Mullen Journal: Diabetologia Date: 2011-05-13 Impact factor: 10.122
Authors: Susan J Burke; Matthew R Goff; Barrett L Updegraff; Danhong Lu; Patricia L Brown; Steven C Minkin; John P Biggerstaff; Ling Zhao; Michael D Karlstad; J Jason Collier Journal: PLoS One Date: 2012-10-09 Impact factor: 3.240