Kato M, Ma H T, Tatemoto K
Department of Physiology, Gunma University, Maebashi, Japan.
Regul Pept. 1996 Apr 9;62(1):23-7. doi: 10.1016/0167-0115(95)00164-6.
An intestinal hormone glucagon-like-peptide-1 (GLP-1) is a prominent candidate for incretin. In vitro experiment showed (Fridolf and Ahren, Mol. Cell. Endocrinol., 96 (1993) 85-90) that GLP-1 increased both insulin secretion and the efflux of 45Ca2+ in a Na(+)-dependent manner. Further, GLP-1 depolarizes the pancreatic beta cells in the presence of high concentration of glucose. Here, we report the effect of GLP-1 on the membrane potential with a physiological concentration of glucose in perforated patch clamp of primary cultured rat beta cells. 10 nM GLP-1 depolarized the beta cell, which was completely reversed by replacing Na+ with the impermeant molecule N-methyl-D-glucamine (NMDG). The Ca2+ channel blocker, Co2+ suppressed the Ca2+ spikes without hyperpolarizing the cell. GLP-1-induced insulin secretion in perifused islets was also suppressed by a prior replacement of Na+ with NMDG. In addition, GLP-1 slightly augmented the long-lasting Ba2+ current, which was reverted to the control level by a selective inhibitor of protein kinase A, H-89. These results indicate: (i) GLP-1 depolarizes the beta cell by activating the membrane Na+ permeability; (ii) GLP-1 slightly modulates the L-type Ca2+ channel probably through protein kinase A; and (iii) at least in part, these mechanisms may be involved in the insulin secretion induced by GLP-1.
一种肠道激素胰高血糖素样肽-1（GLP-1）是肠促胰岛素的一个重要候选者。体外实验表明（弗里多夫和阿伦，《分子与细胞内分泌学》，96（1993）85 - 90），GLP-1以Na⁺依赖的方式增加胰岛素分泌和⁴⁵Ca²⁺外流。此外，在高浓度葡萄糖存在的情况下，GLP-1使胰腺β细胞去极化。在此，我们报告在原代培养大鼠β细胞的穿孔膜片钳实验中，生理浓度葡萄糖条件下GLP-1对膜电位的影响。10 nM GLP-1使β细胞去极化，用非通透分子N-甲基-D-葡糖胺（NMDG）替代Na⁺可使其完全逆转。Ca²⁺通道阻滞剂Co²⁺抑制Ca²⁺峰而不使细胞超极化。预先用NMDG替代Na⁺也可抑制GLP-1诱导的灌流胰岛中的胰岛素分泌。此外，GLP-1轻微增强了持久的Ba²⁺电流，蛋白激酶A的选择性抑制剂H-89可使其恢复到对照水平。这些结果表明：（i）GLP-1通过激活膜Na⁺通透性使β细胞去极化；（ii）GLP-1可能通过蛋白激酶A轻微调节L型Ca²⁺通道；（iii）至少部分地，这些机制可能参与GLP-1诱导的胰岛素分泌。
