کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2536207 1559143 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Clioquinol attenuates zinc-dependent β-cell death and the onset of insulitis and hyperglycemia associated with experimental type I diabetes in mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Clioquinol attenuates zinc-dependent β-cell death and the onset of insulitis and hyperglycemia associated with experimental type I diabetes in mice
چکیده انگلیسی

Zinc in the pancreas is co-released with insulin from β-cells reaching concentrations similar to those found in the vicinity of glutamatergic synapses. In the brain, the role of zinc in excitotoxic brain damage is well established. In contrast, its role in islet destruction during diabetes is poorly understood. We have studied the efficacy of zinc homeostatic proteins and an intracellular zinc chelator, clioquinol, in conferring resistance against zinc toxicity in pancreatic islets. We further assessed the ability of clioquinol to protect the islets in an experimental model of type I diabetes. Our results indicate that endogenous mechanisms for lowering [Zn]i are deficient in the insulinoma cell line, MIN6, and that permeation of Zn2+ triggered cell death. Application of the low affinity, intracellular zinc chelator, clioquinol, reduced Zn2+-induced cell death by 80%. In addition, chelation of zinc ions by clioquinol in vivo prevented onset of multiple low dose streptozotocin-induced diabetes, and reduced the insulitis and hyperglycemia associated with this model. Furthermore, the glucose tolerance test (GTT) score of multiple low dose streptozotocin (MLD-STZ) mice pretreated with clioquinol was, statistically indistinguishable from that of untreated, control mice. Taken together, our results point to the potential utility of in vivo zinc chelation as a therapeutic strategy for treatment of idiopathic type I diabetes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 565, Issues 1–3, 22 June 2007, Pages 232–239
نویسندگان
, , ,