Noda M, Komatsu M, Sharp G W
Department of Pharmacology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Diabetes. 1996 Dec;45(12):1766-73. doi: 10.2337/diab.45.12.1766.
betaHC-9 is a pancreatic beta-cell line that is derived from the hyperplastic islets of transgenic mice that express the simian virus 40 tumor antigen gene in the islets. This cell secretes insulin in response to glucose in a concentration-dependent manner. Maximal and half-maximal concentrations were approximately 20 and approximately 10 mmol/l, respectively, with a maximal fractional release that averaged 3.7% of the total cellular insulin content per 60 min. The cellular insulin content was 3-9% of the content of mouse islet cells. Under perifusion conditions, high glucose concentrations induced a sharp first phase that lasted approximately 10 min and a succeeding second phase of sustained release, as exhibited by mouse islets. The cells did not show a rising second phase as seen with rat islets. This biphasic response was obtained without the need for activators of protein kinase A such as forskolin or 3-isobutyl-1-methylxanthine. The dose-dependency and the phasic response to glucose were essentially invariable up to passage 38 but thereafter declined. The cells respond to various well-known stimulators of insulin secretion, including leucine and arginine; to modulators such as carbachol, glucagon-like peptide I, and pituitary adenylyl cyclase activating polypeptide; and to the inhibitors norepinephrine, somatostatin, and galanin. The pharmacological agents glibenclamide, 12-O-tetradecanoylphorbol-13-acetate, and KCl stimulate and forskolin potentiates insulin release. Mannoheptulose, 2-deoxyglucose, and nitrendipine inhibit glucose-stimulated insulin release from the cells. The intracellular Ca2+ concentration was raised by high glucose and by glibenclamide. In conclusion, this cell line preserves the fundamental characteristics of the progenitor normal mouse islets very well. Although several cell lines have been reported to have glucose-responsive insulin secretion, few demonstrate clear biphasic secretion as this cell line displays. In this context, this cell line should serve as a potent tool for studying the mechanisms of insulin secretion, especially the important phasic secretion.
βHC - 9是一种胰腺β细胞系，它源自转基因小鼠的增生胰岛，这些转基因小鼠的胰岛中表达了猿猴病毒40肿瘤抗原基因。该细胞以浓度依赖的方式对葡萄糖作出反应并分泌胰岛素。最大浓度和半最大浓度分别约为20 mmol/L和约10 mmol/L，最大分数释放平均为每60分钟细胞总胰岛素含量的3.7%。细胞内胰岛素含量为小鼠胰岛细胞含量的3% - 9%。在灌流条件下，高葡萄糖浓度诱导出一个持续约10分钟的急剧的第一相以及随后的持续释放的第二相，这与小鼠胰岛的表现相同。这些细胞没有像大鼠胰岛那样出现上升的第二相。这种双相反应无需蛋白激酶A激活剂（如福斯可林或3 - 异丁基 - 1 - 甲基黄嘌呤）即可获得。直到第38代，对葡萄糖的剂量依赖性和相反应基本不变，但此后有所下降。这些细胞对各种已知的胰岛素分泌刺激物有反应，包括亮氨酸和精氨酸；对调节剂如卡巴胆碱、胰高血糖素样肽I和垂体腺苷酸环化酶激活多肽有反应；对抑制剂去甲肾上腺素、生长抑素和甘丙肽有反应。药物格列本脲、12 - O - 十四酰佛波醇 - 13 - 乙酸酯和氯化钾刺激胰岛素释放，福斯可林增强胰岛素释放。甘露庚酮糖、2 - 脱氧葡萄糖和尼群地平抑制细胞对葡萄糖刺激的胰岛素释放。高葡萄糖和格列本脲可提高细胞内Ca2 +浓度。总之，该细胞系很好地保留了祖代正常小鼠胰岛的基本特征。尽管已有报道几种细胞系具有葡萄糖反应性胰岛素分泌，但很少有细胞系像该细胞系那样表现出明显的双相分泌。在这种情况下，该细胞系应成为研究胰岛素分泌机制，尤其是重要的相分泌机制的有力工具。
