Troglitazone can prevent development of type 1 diabetes induced by multiple low-dose streptozotocin in mice
1999; Elsevier BV; Volume: 65; Issue: 12 Linguagem: Inglês
10.1016/s0024-3205(99)00364-1
ISSN1879-0631
AutoresJunko Ogawa, Sayaka Takahashi, Toshihiko Fujiwara, Junichiro Fukushige, Tsunemichi Hosokawa, Takashi Izumi, Shinichi Kurakata, Hiroyoshi Horikoshi,
Tópico(s)Diet, Metabolism, and Disease
ResumoRecent investigations suggest that cytotoxic cytokines such as tumor necrosis factor (TNF)α and interleukin (IL)-1β or free radicals play an essential role in destruction of pancreatic β cells in Type 1 diabetes and that, therefore, anti-oxidant or anti-TNFα and IL-1β therapy could prevent the development of Type I diabetes. Troglitazone belongs to a novel class of antidiabetic agent possessing the ability to enhance insulin action provably through activating PPAR γ and to scavenge free radicals. In the present study, we examined whether troglitazone can prevent the development of Type 1 diabetes in multiple, low-dose streptozotocin (MLDSTZ)-injected mice, hi addition, effects of troglitazone on cytokine-induced pancreatic β cell damage were examined in vitro. Type 1 diabetes was induced by MLDSTZ injection to DBA2 mice (40 mg/kg/day for 5 days). Troglitazone was administered as a 0.2% food admixture (240 mg/kg/day) for 4 weeks from the start of or immediately after STZ injection. MLDSTZ injection elevated plasma glucose to 615 ± 8 mgdl 4 weeks after final STZ injection and was accompanied by infiltration of leukocytes to pancreatic islets (insulitis). Troglitazone treatment with MLDSTZ injection prevented hyperglycemia (230 ± 30 mgdl) and, suppressed insulitis and TNFα production from intraperitoneal exudate cells. TNFα (10 pgml) and IL-1β (1 pgml) addition to hamster insulinoma cell line HIT-T15 for 7 days in vitro decreased insulin secretion and cell viability. Simultaneous troglitazone addition (0.03 ~ 3 μM) significantly improved cytokine-induced decrease in insulin secretion and in cell viability. These findings suggest that troglitazone prevents the development of Type 1 diabetes in the MLDSTZ model by suppressing insulitis associated with decreasing TNFa production from intraperitoneal exudate cells and the subsequent TNFα and IL-1β-induced β cell damage.
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