Inhibition of voltage-gated potassium channels mediates uncarboxylated osteocalcin-regulated insulin secretion in rat pancreatic β cells

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• 作者：Jingying Gao^a ; ^b ; ^c ; ^{13633513158@163.com" class="auth_mail" title="E-mail the corresponding author} ; Xiangqin Zhong^a ; ^{1246131750@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Yaqin Ding^a ; ^{wding041225@163.com" class="auth_mail" title="E-mail the corresponding author} ; Tao Bai^a ; ^b ; ^d ; ^{baitaoy@163.com" class="auth_mail" title="E-mail the corresponding author} ; Hui Wang^a ; ^{1074684265@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Hongbin Wu^e ; ^{whb196910@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yunfeng Liu^d ; ^{nectarliu@163.com" class="auth_mail" title="E-mail the corresponding author} ; Jing Yang^d ; ^{yangjlm@126.com" class="auth_mail" title="E-mail the corresponding author} ; Yi Zhang^a ; ^b ; ^{yizhang313@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：NaCl (PubChem CID ; 5234) ; KH2PO4 (PubChem CID ; 516951) ; KCl (PubChem CID ; 4873) ; CaCl2· ; 2H2O (PubChem CID ; 6093260) ; HEPES (PubChem CID ; 23831) ; Tetraethylammonium chloride (PubChem CID ; 5946) ; Poly-d-lysine hydrobromide (PubChem CID ; 16219815) ; EGTA (PubChem CID ; 6207) ; CsCl (PubChem CID ; 24293) ; Fluo 4AM (PubChem CID ; 4060965)
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：777
• 期：Complete
• 页码：41-48
• 全文大小：912 K

文摘

Insulin secretion from pancreatic β cells is important to maintain glucose homeostasis and is regulated by electrical activities. Uncarboxylated osteocalcin, a bone-derived protein, has been reported to regulate glucose metabolism by increasing insulin secretion, stimulating β cell proliferation and improving insulin sensitivity. But the underlying mechanisms of uncarboxylated osteocalcin-modulated insulin secretion remain unclear. In the present study, we investigated the relationship of uncarboxylated osteocalcin-regulated insulin secretion and voltage-gated potassium (K_V) channels, voltage-gated calcium channels in rat β cells. Insulin secretion was measured by radioimmunoassay. Channel currents and membrane action potentials were recorded using the conventional whole-cell patch-clamp technique. Calcium imaging system was used to analyze intracellular Ca²⁺ concentration ([Ca²⁺]_i). The data show that under 16.7 mmol/l glucose conditions uncarboxylated osteocalcin alone increased insulin secretion and [Ca²⁺]_i, but with no such effects on insulin secretion and [Ca²⁺]_i in the presence of a K_V channel blocker, tetraethylammonium chloride. In the patch-clamp experiments, uncarboxylated osteocalcin lengthened action potential duration and significantly inhibited K_V currents, but had no influence on the characteristics of voltage-gated calcium channels. These results indicate that K_V channels are involved in uncarboxylated osteocalcin-regulated insulin secretion in rat pancreatic β cells. By inhibiting K_V channels, uncarboxylated osteocalcin prolongs action potential duration, increases intracellular Ca²⁺ concentration and finally promotes insulin secretion. This finding provides new insight into the mechanisms of osteocalcin-modulated insulin secretion.