Abstract：
:Agmatine, an endogenous ligand of imidazoline receptors, is reported to exhibit anti-hyperglycaemic and many other effects. It has been established that the imidazoline I3 receptor is involved in insulin secretion. The current study characterizes the role of the imidazoline I3 receptor in the protection of pancreatic islets. The activity effect of agmatine against on streptozotocin (STZ)-induced (5 mmol/L) rat β cell apoptosis was examined by using ApoTox-Glo triplex assay, live/dead cell double staining assay, flow cytometric analysis, and western blot. Imidazoline I3 receptors antagonist KU14R and the phospholipase C inhibitor named U73122 were treated in β cells to investigate the potential signalling pathways. The serum glucose and recovery of insulin secretion were measured in STZ-treated rats after continuously injected agmatine. The apoptosis in rat β cells was reduced by agmatine in a dose-dependent manner, cell viability was improved after treatment with agmatine and these effects were suppressed after the blockade of KU14R and U73122. Western blot analysis confirmed that agmatine could decrease caspase-3 expression and increase the p-BAD levels. In STZ-treated rats, injection of agmatine for 4 weeks may significantly lower the serum glucose and recovery of insulin secretion. This improvement of pancreatic islets induced by agmatine was deleted by KU14R in vivo. Agmatine can activate the imidazoline I3 receptor linked with the phospholipase C pathway to induce cell protection against apoptosis induced by a low dose of STZ. This finding provides new insight into the prevention of early stage pancreatic islet damage.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Li Y,Cheng KC,Asakawa A,Amitani H,Takimoto Y,Runtuwene J,Inui Adoi
10.1111/1440-1681.12441subject
Has Abstractpub_date
2015-09-01 00:00:00pages
964-971issue
9eissn
0305-1870issn
1440-1681journal_volume
42pub_type
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