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小鼠胰腺β细胞和胰岛代谢振荡的比较。

Comparison of metabolic oscillations from mouse pancreatic beta cells and islets.

作者信息

Nunemaker Craig S, Satin Leslie S

机构信息

Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA.

出版信息

Endocrine. 2004 Oct;25(1):61-7. doi: 10.1385/ENDO:25:1:61.

Abstract

Rhythmic insulin secretion from pancreatic islets is the culmination of many processes both intrinsic and extrinsic to the beta cell. We wished to examine and compare endogenous metabolic oscillations in islets and isolated single beta cells that underlie secretion. Fluorescence patterns of rhodamine 123, an indicator of mitochondrial membrane potential (DeltaPsim), were analyzed for period and amplitude of oscillations using two methods: CLUSTER7 and fast Fourier transform (FFT). The period of DeltaPsim oscillations was greater in islets (271 +/- 21 s, n = 34) compared to dispersed beta cells (180 +/- 10 s, n = 54) by FFT analysis (p < 0.0005). CLUSTER7 confirmed differences in period and also detected oscillatory amplitude differences between beta cells (12.0 +/- 0.8) and islets (7.1 +/- 2.3% of baseline fluorescence, p < 0.0001). Depolarizing responses to the mitochondrial poison NaN3 were reduced in beta cells (35 +/- 4%) vs islets (58 +/- 9%), and hyperpolarizing responses to the calcium channel blocker nifedipine were enhanced in beta cells (15 +/- 4%) vs islets (8 +/- 1%), suggesting that mitochondria in dispersed beta cells were less energized than those in intact islets (p < 0.005), possibly due to elevated intracellular calcium. These findings suggest that individual beta cells possess the proper machinery to generate metabolic oscillations. Differences in oscillatory period, DeltaPsim, and nifedipine response suggest that incorporation into islets provides beta cells with additional modulatory influences.

摘要

胰岛有节奏地分泌胰岛素是β细胞许多内在和外在过程的最终结果。我们希望研究和比较胰岛和分离的单个β细胞中作为分泌基础的内源性代谢振荡。使用两种方法(CLUSTER7和快速傅里叶变换(FFT))分析了作为线粒体膜电位(ΔΨm)指标的罗丹明123的荧光模式,以确定振荡的周期和幅度。通过FFT分析,与分散的β细胞(180±10秒,n = 54)相比,胰岛中ΔΨm振荡的周期更长(271±21秒,n = 34)(p < 0.0005)。CLUSTER7证实了周期差异,还检测到β细胞(12.0±0.8)和胰岛(基线荧光的7.1±2.3%,p < 0.0001)之间的振荡幅度差异。β细胞对线粒体毒物NaN3的去极化反应(35±4%)低于胰岛(58±9%),而β细胞对钙通道阻滞剂硝苯地平的超极化反应(15±4%)高于胰岛(8±1%),这表明分散的β细胞中的线粒体比完整胰岛中的线粒体能量更低(p < 0.005),可能是由于细胞内钙升高所致。这些发现表明单个β细胞具备产生代谢振荡的适当机制。振荡周期、ΔΨm和硝苯地平反应的差异表明,整合到胰岛中为β细胞提供了额外的调节影响。

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