Multidisciplinary Research Center, Shantou University, Shantou, Guangdong, China.
Pancreas. 2011 May;40(4):615-21. doi: 10.1097/MPA.0b013e31820b4b23.
Chronic administration of nicotinic acid (NA), a potent antilipidemic compound, aggravates glycemic control in diabetic patients. It is not known if NA has direct effects on islet β cells.
Real-time reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunofluorescence techniques were used to examine the expression of NA receptor PUMA-G, a member of the G protein-coupled receptor (G-PCR) family, in murine islet β cells. Calcium transient was measured using confocal microscopy, whereas the intracellular cyclic adenosine monophosphate and glucose-stimulated insulin secretion (GSIS) from isolated islets were determined by the enzyme-linked immunosorbent assay.
High levels of PUMA-G transcripts and protein were detected in all β cells, and about 40% of α cells. PUMA-G transcripts increased more than 3-fold in islets incubated with interferon γ. Cyclic adenosine monophosphate accumulation, induced by IBMX/forskolin, was inhibited by NA; however, the inhibition was completely abolished by pretreatment of the culture with pertussis toxin. No calcium transient was detected in islet cells in the presence of NA. Static incubation of islets with NA led to an approximately 30% reduction of GSIS.
The results indicated that PUMA-G stimulation by NA in islet β cells inhibited GSIS likely via activation of the Gi signaling pathway.
烟酸（NA）是一种有效的抗脂化合物，长期给药会加重糖尿病患者的血糖控制。目前尚不清楚 NA 是否对胰岛β细胞有直接作用。
采用实时逆转录-聚合酶链反应、原位杂交和免疫荧光技术检测 G 蛋白偶联受体（GPCR）家族成员烟碱型乙酰胆碱受体亚单位基因 PUMA-G 在小鼠胰岛β细胞中的表达。应用共聚焦显微镜检测钙瞬变，通过酶联免疫吸附试验测定分离胰岛的细胞内环腺苷酸（cAMP）和葡萄糖刺激的胰岛素分泌（GSIS）。
在所有β细胞和约 40%的α细胞中均检测到高水平的 PUMA-G 转录本和蛋白。与干扰素γ孵育的胰岛中，PUMA-G 转录本增加了 3 倍以上。IBMX/佛波醇诱导的 cAMP 积累被 NA 抑制；然而，用百日咳毒素预处理培养物可完全消除抑制作用。在 NA 存在的情况下，胰岛细胞中未检测到钙瞬变。胰岛的静态孵育导致 GSIS 降低约 30%。
结果表明，NA 刺激胰岛β细胞中的 PUMA-G 可能通过激活 Gi 信号通路抑制 GSIS。
