Streptozotocin (STZ) is used widely in experimental animal models of type 1 diabetes. STZ is a β-cell-specific toxin that induces irreversible and rapid apoptosis of pancreatic β-cells. Abstract. Resveratrol (3,5,4′-trihydroxystilbene; RSV) is one kind of polyphenolic phytoalexin that has many effects on metabolic diseases. This study aimed to evaluate the protective effect of RSV pretreatment on β-cell. Male Sprague Dawley rats weighing 200-230 g were divided into 4 groups: (1) RSV; (2) streptozotocin (STZ, 70 mg/kg, intraperitoneally); (3) STZ after 7 days pretreatment with RSV; and (4) STZ pretreated with nicotinamide. Fasting glucose concentration was measured and an intraperitoneal glucose tolerance test was performed 72 h after STZ injection to determine the diabetic condition. The pancreas was removed 3, 6, 36, and 48 h after STZ injection. STZ induced diabetes in all rats not given RSV pretreatment, whereas none of the RSV-pretreated rats developed diabetes. Pretreatment with RSV inhibited apoptosis and reduced the activation of caspase-3 and poly(ADP-ribose) polymerase (PARP). However, expression of the total length PARP was not affected by pretreatment. Our findings suggest that RSV protects β-cells from STZ simultaneously with inhibiting the activation of PARP.
Islet transplantation is a potential treatment for type 1 diabetes. Currently, islet graft survival is measured using invasive methods to determine blood glucose, insulin, and C-peptide levels, even though these variables have limited value. To trace beta-cell survival and functional status, we constructed an adenovirus/adenoassociate virus hybrid vector (Hyb-DR) carrying two reporter genes, luciferase and green fluorescent protein (GFP), linked by the internal ribosome entry site and driven by the rat insulin II promoter. Luciferase activity increased and positive GFP expression was observed in beta-cell lines (MIN6N8 and INS-1E) infected with Hyb-DR. Using an in vivo imaging instrument, the GFP signal was detected in the flanks of nude mice 2 weeks after transplanting Hyb-DR-infected MIN6 cells into the kidney capsule. Coinfection of Hyb-DR with plasmids carrying beta-cell-specific transcription factors also resulted in expression of luciferase and GFP in the non-beta-cell lines (HepG2, FL83B, and YGIC5). Thus, the dual reporter system provided quantitative and visual information about the functionality of the islet mass and activation of the insulin gene.
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