Curcumin pretreatment mediates antidiabetogenesis via functional regulation of adrenergic receptor subtypes in the pancreas of multiple low-dose streptozotocin-induced diabetic rats

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• 作者：George Naijil ; T.R. Anju ; S. Jayanarayanan ; C.S. Paulose ; ^{cspaulose@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; ^{cspaulose@cusat.ac.in" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Curcumin ; Diabetes ; Adrenergic receptor ; Pancreas ; 尾 Cell
• 刊名：Nutrition Research
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：35
• 期：9
• 页码：823-833
• 全文大小：862 K

文摘

Lifestyle modification pivoting on nutritional management holds tremendous potential to meet the challenge of management of diabetes. The current study hypothesizes that regular uptake of curcumin lowers the incidence of diabetes by functional regulation of pancreatic adrenergic receptor subtypes. The specific objective of the study was to identify the regulatory pathways implicated in the antidiabetogenesis effect of curcumin in multiple low-dose streptozotocin (MLD-STZ)-induced diabetic Wistar rats. Administration of MLD-STZ to curcumin-pretreated rats induced a prediabetic condition. Scatchard analysis, real-time polymerase chain reaction, and confocal microscopic studies confirmed a significant increase in 伪₂-adrenergic receptor expression in the pancreas of diabetic rats. Pretreatment with curcumin significantly decreased 伪₂-adrenergic receptor expression. The diabetic group showed a significant decrease in the expression of 尾-adrenergic receptors when compared with control. Pretreatment significantly increased 尾-adrenergic receptor expression to near control. When compared with the diabetic rats, a significant up-regulation of CREB, phospholipase C, insulin receptor, and glucose transporter 2 were observed in the pretreated group. Curcumin pretreatment was also able to maintain near control levels of cyclic adenosine monophosphate, cyclic guanosine monophosphate, and inositol triphosphate. These results indicate that a marked decline in 伪₂-adrenergic receptor function relents sympathetic inhibition of insulin release. It also follows that escalated signaling through 尾-adrenergic receptors mediates neuronal stimulation of hyperglycemia-induced 尾-cell compensatory response. Curcumin-mediated functional regulation of adrenergic receptors and modulation of key cell signaling molecules improve pancreatic glucose sensing, insulin gene expression, and insulin secretion.