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Inhibition of Voltage-Gated Potassium Channels Mediates Uncarboxylated Osteocalcin-Regulated Insulin Secretion in Rat Pancreatic β Cells

Inhibition of Voltage-Gated Potassium Channels Mediates Uncarboxylated Osteocalcin-Regulated Insulin Secretion in Rat Pancreatic β Cells

Jingying Gao, Xiangqin Zhong, Yaqin Ding, Tao Bai, Hui Wang, Hongbin Wu, Yunfeng Liu, Jing Yang, Yi Zhang

Eur J Pharmacol. 2016 Apr 15;777:41-8.

PMID: 26927753

Abstract:

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 (KV) 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 Ca(2+) concentration ([Ca(2+)]i). The data show that under 16.7mmol/l glucose conditions uncarboxylated osteocalcin alone increased insulin secretion and [Ca(2+)]i, but with no such effects on insulin secretion and [Ca(2+)]i in the presence of a KV channel blocker, tetraethylammonium chloride. In the patch-clamp experiments, uncarboxylated osteocalcin lengthened action potential duration and significantly inhibited KV currents, but had no influence on the characteristics of voltage-gated calcium channels. These results indicate that KV channels are involved in uncarboxylated osteocalcin-regulated insulin secretion in rat pancreatic β cells. By inhibiting KV channels, uncarboxylated osteocalcin prolongs action potential duration, increases intracellular Ca(2+) concentration and finally promotes insulin secretion. This finding provides new insight into the mechanisms of osteocalcin-modulated insulin secretion.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP27964994	Poly-D-lysine hydrobromide		27964-99-4	Price

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