Lee B, Jonas J C, Weir G C, Laychock S G
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, the State University of New York at Buffalo, 14214, USA.
Endocrinology. 1999 May;140(5):2173-82. doi: 10.1210/endo.140.5.6738.
Isolated rat pancreatic islets were studied to determine the dynamic regulatory effects of glucose stimulation on the expression of messenger RNA (mRNA) and protein levels for inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) isoforms I, II, and III. The relative isoform abundance was: IP3R-III > IP3R-II approximately IP3R-I. Culture of islets with glucose (G; 20 mM) or alpha-ketoisocaproic acid for 30 min increased only IP3R-III mRNA expression above control (5.5 mM glucose). 2-Deoxyglucose was without effect. Islet culture for 2 h with G (20 mM) or alpha-ketoisocaproic acid reduced IP3R-III mRNA expression levels below control, and cycloheximide blocked the response. Culturing islets for 1 day or 7 days with G (11 mM) reduced the expression of IP3R-III mRNA but increased the expression of IP3R-II mRNA in a time-dependent manner. Cytosine arabinoside lowered cultured islet IP3R-II and -III mRNA levels, but glucose effects remained evident. IP3R-II mRNA levels were also significantly higher in islets from hyperglycemic 90% partial pancreatectomized rats, compared with sham animals. Islet IP3R mRNA expression also showed osmotic sensitivity. Islet IP3R-III protein levels increased after 2 h islet culture at 20 mM G, were unchanged after 1 day culture at 11 mM G, and were lower than control after 7 days culture at 11 mM G. In contrast, IP3R-II levels increased after 1 day and 7 days culture at 11 mM G, whereas IP3R-I protein levels remained unchanged. Thus, G stimulation rapidly increases transcription and expression of IP3R-III mRNA and protein levels in rat islets. However, chronic G stimulation up-regulates IP3R-II mRNA in cultured islets and in islets from partial pancreatectomized rats. Metabolic regulation of IP3R-II and III expression may mediate beta-cell IP3-responsive Ca2+ mobilization and insulin secretion.
研究分离的大鼠胰岛，以确定葡萄糖刺激对1,4,5-三磷酸肌醇（IP3）受体I、II和III亚型的信使核糖核酸（mRNA）表达和蛋白质水平的动态调节作用。各亚型的相对丰度为：IP3R-III>IP3R-II≈IP3R-I。用葡萄糖（G；20 mM）或α-酮异己酸培养胰岛30分钟，仅使IP3R-III mRNA表达高于对照（5.5 mM葡萄糖）。2-脱氧葡萄糖无作用。用G（20 mM）或α-酮异己酸培养胰岛2小时，使IP3R-III mRNA表达水平低于对照，放线菌酮可阻断该反应。用G（11 mM）培养胰岛1天或7天，可降低IP3R-III mRNA表达，但以时间依赖方式增加IP3R-II mRNA表达。阿糖胞苷降低培养胰岛的IP3R-II和-III mRNA水平，但葡萄糖的作用仍然明显。与假手术动物相比，高血糖90%胰腺部分切除大鼠的胰岛中IP3R-II mRNA水平也显著更高。胰岛IP3R mRNA表达也表现出渗透压敏感性。在20 mM G下培养胰岛2小时后，IP3R-III蛋白水平升高，在11 mM G下培养1天后不变，在11 mM G下培养7天后低于对照。相反，在11 mM G下培养1天和7天后，IP3R-II水平升高，而IP3R-I蛋白水平保持不变。因此，G刺激可迅速增加大鼠胰岛中IP3R-III mRNA和蛋白水平的转录和表达。然而，慢性G刺激可上调培养胰岛和部分胰腺切除大鼠胰岛中的IP3R-II mRNA。IP3R-II和III表达的代谢调节可能介导β细胞IP3反应性Ca2+动员和胰岛素分泌。
