Physiological levels of adrenaline fail to stop pancreatic beta cell activity at unphysiologically high glucose levels.
Physiological levels of adrenaline fail to stop pancreatic beta cell activity at unphysiologically high glucose levels.
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DOI：
10.3389/fendo.2022.1013697
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发表时间：
2022
影响因子：
5.2
通讯作者：
Rupnik, Marjan Slak
中科院分区：
文献类型：
--
作者：
Sluga, Nastja;Bombek, Lidija Krizancic;Kercmar, Jasmina;Sarikas, Srdjan;Postic, Sandra;Pfabe, Johannes;Skelin Klemen, Masa;Korosak, Dean;Stozer, Andraz;Rupnik, Marjan Slak
肾上腺素抑制胰腺β细胞分泌胰岛素，使生物体通过释放内部营养储备来满足即时的能量需求。 β 细胞质膜上 α2-肾上腺素能受体的刺激主要通过减少 cAMP 产生和胞吐机制后期步骤对胞质 Ca2+ 浓度 ([Ca2+]c) 的下游脱敏来降低其兴奋性和胰岛素分泌。在大多数研究中，非生理性高肾上腺素浓度已被用来评估肾上腺素能刺激对胰腺内分泌细胞的作用。在这里，我们报告了生理肾上腺素水平对小鼠胰腺组织切片制备中β细胞群中[Ca2+]c动力学的影响。我们使用具有高空间和时间分辨率的共聚焦显微镜来评估葡萄糖刺激的 [Ca2+]c 事件及其对肾上腺素的敏感性。我们研究了 8-20 mM 的葡萄糖浓度，以评估完全消除 [Ca2+]c 事件的肾上腺素浓度。我们发现，生理条件下可用的肾上腺素浓度很容易抑制 8 mM 葡萄糖对 β 细胞集体的刺激，并且随后用高 nM 范围内的 12 mM 葡萄糖或毛喉素进行刺激会克服这种抑制。因此，12 mM 葡萄糖刺激需要比生理水平高出至少一个数量级的肾上腺素浓度才能抑制活性。总之，较高的葡萄糖浓度以非线性方式刺激β细胞活性，并且超出了生理上可用的血浆肾上腺素浓度可以抑制的水平。
Adrenaline inhibits insulin secretion from pancreatic beta cells to allow an organism to cover immediate energy needs by unlocking internal nutrient reserves. The stimulation of α2-adrenergic receptors on the plasma membrane of beta cells reduces their excitability and insulin secretion mostly through diminished cAMP production and downstream desensitization of late step(s) of exocytotic machinery to cytosolic Ca2+ concentration ([Ca2+]c). In most studies unphysiologically high adrenaline concentrations have been used to evaluate the role of adrenergic stimulation in pancreatic endocrine cells. Here we report the effect of physiological adrenaline levels on [Ca2+]c dynamics in beta cell collectives in mice pancreatic tissue slice preparation. We used confocal microscopy with a high spatial and temporal resolution to evaluate glucose-stimulated [Ca2+]c events and their sensitivity to adrenaline. We investigated glucose concentrations from 8-20 mM to assess the concentration of adrenaline that completely abolishes [Ca2+]c events. We show that 8 mM glucose stimulation of beta cell collectives is readily inhibited by the concentration of adrenaline available under physiological conditions, and that sequent stimulation with 12 mM glucose or forskolin in high nM range overrides this inhibition. Accordingly, 12 mM glucose stimulation required at least an order of magnitude higher adrenaline concentration above the physiological level to inhibit the activity. To conclude, higher glucose concentrations stimulate beta cell activity in a non-linear manner and beyond levels that could be inhibited with physiologically available plasma adrenaline concentration.
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肾上腺素通过增加 Ca2+ 电流和靠近 L 型 Ca2+ 通道的颗粒数量来刺激胰腺 A 细胞的胰高血糖素分泌。
影响因子：
3.8
作者：
Gromada, J;Bokvist, K;Ding, WG;Barg, S;Buschard, K;Renstrom, E;Rorsman, P
通讯作者：
Rorsman, P
影响因子：
5
作者：
AHREN, B;LUNDQUIST, I
通讯作者：
LUNDQUIST, I
影响因子：
56.9
作者：
CHARLES, MA;FANSKA, R;GRODSKY, GM
通讯作者：
GRODSKY, GM
DOI：
10.1113/expphysiol.1983.sp002716
发表时间：
1983-01-01
影响因子：
--
作者：
DESA, SS;FERRER, R;ATWATER, I
通讯作者：
ATWATER, I
影响因子：
9.8
作者：
HIROSE, H;MARUYAMA, H;SARUTA, T
通讯作者：
SARUTA, T