Flatt P R, Shiber O, Hampton S M, Marks V
Department of Biological and Biomedical Sciences, University of Ulster, Coleraine, UK.
Diabetes Res. 1990 Feb;13(2):55-9.
Insulin-releasing effects of glucagon-like peptides, glucagon and various nutrients were examined using tumour cells from a freshly resected human insulinoma and RINm5F cells. Insulin release by human insulinoma cells or RINm5F cells was not affected by 16.7 mM glucose. Both cell types exhibited secretory responses to 20 mM alanine, 25 mM K+ and 7.6 mM Ca2+. Insulin release by human insulinoma cells was enhanced at 2 x 10(-7) M by glucagon, GLP-1[1-37], GLP-1[7-36] and its N- and C-terminal fragments GLP-1[7-14] and GLP-1[31-37]. The intact peptides (2 x 10(-6)-2 x 10(-12) M) also stimulated insulin release by RINm5F cells, but neither of the fragments enhanced secretion. The cyclic AMP content of human insulinoma cells and RINm5F cells was increased by glucagon. GLP-1[7-36] (2 x 10(-8)-2 x 10(-10) M) increased cyclic AMP in RINm5F cells, but no additional effects were noted in these or human insulinoma cells. These results suggest that GLP-1[7-36] stimulates insulin release by a direct action on human and rat B-cells, partly involving modulation of intracellular cyclic AMP.
利用来自新鲜切除的人胰岛素瘤的肿瘤细胞和RINm5F细胞，研究了胰高血糖素样肽、胰高血糖素和各种营养物质的胰岛素释放作用。人胰岛素瘤细胞或RINm5F细胞的胰岛素释放不受16.7 mM葡萄糖的影响。两种细胞类型对20 mM丙氨酸、25 mM K+和7.6 mM Ca2+均表现出分泌反应。胰高血糖素、GLP-1[1-37]、GLP-1[7-36]及其N端和C端片段GLP-1[7-14]和GLP-1[31-37]可使2×10(-7)M时人胰岛素瘤细胞的胰岛素释放增加。完整肽（2×10(-6)-2×10(-12)M）也刺激RINm5F细胞释放胰岛素，但两个片段均未增强分泌。胰高血糖素可增加人胰岛素瘤细胞和RINm5F细胞的环磷酸腺苷含量。GLP-1[7-36]（2×10(-8)-2×10(-10)M）可增加RINm5F细胞中的环磷酸腺苷，但在这些细胞或人胰岛素瘤细胞中未观察到其他作用。这些结果表明，GLP-1[7-36]通过直接作用于人及大鼠的B细胞刺激胰岛素释放，部分涉及细胞内环磷酸腺苷的调节。
