2. Academic Validation
  3. The PLC/PKC/Ras/MEK/Kv channel pathway is involved in uncarboxylated osteocalcin-regulated insulin secretion in rats

The PLC/PKC/Ras/MEK/Kv channel pathway is involved in uncarboxylated osteocalcin-regulated insulin secretion in rats

  • Peptides. 2016 Dec;86:72-79. doi: 10.1016/j.peptides.2016.10.004.
Jingying Gao 1,  Tao Bai 2,  Lele Ren 3,  Yaqin Ding 3,  Xiangqin Zhong 3,  Hui Wang 3,  Yangyan Guo 3,  Jie Li 3,  Yunfeng Liu 4,  Yi Zhang 5
Affiliations

Affiliations

  • 1 Department of Pharmacology, Shanxi Medical University, Taiyuan, China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China; Department of Pediatrics, Shanxi Medical University, Taiyuan, China.
  • 2 Department of Pharmacology, Shanxi Medical University, Taiyuan, China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China; Department of Endocrinology, the First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, China.
  • 3 Department of Pharmacology, Shanxi Medical University, Taiyuan, China.
  • 4 Department of Endocrinology, the First Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, China. Electronic address: nectarliu@163.com.
  • 5 Department of Pharmacology, Shanxi Medical University, Taiyuan, China; Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China. Electronic address: yizhang313@163.com.
PMID: 27746193 DOI: 10.1016/j.peptides.2016.10.004
Abstract

Uncarboxylated osteocalcin, a bone matrix protein, has been proposed to regulate glucose metabolism by increasing Insulin secretion, improving Insulin sensitivity and stimulating β cell proliferation. Our previous study also indicated that uncarboxylated osteocalcin stimulates Insulin secretion by inhibiting voltage-gated potassium (KV) channels. The goal of this study is to further investigate the underlying mechanisms for the regulation of Kv channels and Insulin secretion by uncarboxylated osteocalcin. Insulin secretion and Kv channel currents were examined by radioimmunoassay and patch-clamp technique, respectively. Calcium imaging system was applied to measure intracellular CA2+ concentration ([CA2+]i). The protein levels were detected by western blot. The results showed that uncarboxylated osteocalcin potentiated Insulin secretion, inhibited Kv channels and increased [CA2+]i compared to control. These effects were suppressed by phospholipase-C (PLC)/protein kinase C (PKC)/Ras/MAPK-ERK kinase (MEK) signaling pathway, indicating that this signaling pathway plays an important role in uncarboxylated osteocalcin-regulated insulinotropic effect. In addition, the results also showed that adenylyl cyclase (AC) did not influence the effect of uncarboxylated osteocalcin on Insulin secretion and Kv channels, suggesting that AC is not involved in uncarboxylated osteocalcin-stimulated Insulin secretion. These findings provide new insight into the mechanism of uncarboxylated osteocalcin-regulated Insulin secretion.

Keywords

Insulin secretion; Phospholipase-C; Uncarboxylated osteocalcin; Voltage-gated potassium channel.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z