GLUCOSE-DEPENDENT ALTERATIONS OF INTRACELLULAR FREE CALCIUM BY GLUCAGON-LIKE PEPTIDE-1((7-36AMIDE)) IN INDIVIDUAL OB/OB MOUSE BETA-CELLS
GLUCOSE-DEPENDENT ALTERATIONS OF INTRACELLULAR FREE CALCIUM BY GLUCAGON-LIKE PEPTIDE-1((7-36AMIDE)) IN INDIVIDUAL OB/OB MOUSE BETA-CELLS
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DOI：
10.1016/0143-4160(94)90014-0
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发表时间：
1994-05-01
期刊：
影响因子：
4
通讯作者：
LEIBOWITZ, MD
中科院分区：
文献类型：
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作者：
CULLINAN, CA;BRADY, EJ;LEIBOWITZ, MD
葡萄糖的去极化浓度会产生胰腺 β 细胞中细胞内游离 Ca2+ ([Ca2+](i)) 的特征性改变。所提出的肠降血糖素、胰高血糖素样肽-1((7-36amide)) (GLP-1(a)) 对 [Ca2+](i) 的影响通过培养的 ob/ob 小鼠胰腺 β 细胞的 Fura-2 荧光比成像来确定。在对照细胞中，[Ca2+](i) 在 3 mM 葡萄糖中含量较低；将 [葡萄糖] 增加至 8-12 mM 会导致 [Ca2+](i) 初始下降，随后 [Ca2+](i) 缓慢振荡增加。 GLP-1(a) (0.03-10 000 pM) 不会改变 3 mM 葡萄糖中的 [Ca2+](i)，但会改变对升高葡萄糖 (8-12 mM) 的反应。初始下降的时间积分减少（[GLP-1(a)] 10-100 pM），[Ca2+](i) 信号的积分增加（[GLP-1(a)] 大于或等于 1 pM）。 GLP-1(a) 增加了对升高的葡萄糖持续、稳定的平台反应的频率，以及与平台或振荡相关的 [Ca2+](i) 增加的大而快速的峰值频率。 cAMP 类似物的应用模拟了 GLP-1(a) 的大部分作用。仅当[葡萄糖]较高时，GLP-1(a) 受体的激活或 cAMP 的应用才会改变胰腺 β 细胞 [Ca2+](i)。
Depolarizing concentrations of glucose produce characteristic alterations of intracellular free Ca2+ ([Ca2+](i)) in pancreatic beta-cells. The effects of the proposed incretin, glucagon-like peptide-1((7-36amide)) (GLP-1(a)) on [Ca2+](i) were determined from Fura-2 fluorescence ratio imaging of cultured ob/ob mouse pancreatic beta-cells. In control cells, [Ca2+](i) is low in 3 mM glucose; increasing [glucose] to 8-12 mM results in an Initial dip in [Ca2+](i) followed by slow oscillating increases in [Ca2+](i). GLP-1(a) (0.03-10 000 pM) does not alter [Ca2+](i) in 3 mM glucose, but does change the response to elevated glucose (8-12 mM). The time integral of the initial dip is reduced ([GLP-1(a)] 10-100 pM), and the integral of the [Ca2+](i) signal is increased ([GLP-1(a)] greater than or equal to 1 pM). GLP-1(a) increases the frequency of sustained, stable plateau responses to elevated glucose, and the frequency of large, rapid spikes of increased [Ca2+](i) associated with either plateaus, or oscillations. Application of a cAMP analog mimics most of the actions of GLP-1(a). Activation of the GLP-1(a) receptor, or application of cAMP alters pancreatic beta-cell [Ca2+](i) only when [glucose] is high.