非损伤微测技术----在糖尿病方面的应用

 

北美有大约18亿人罹患2型糖尿病,这些患者中年龄最小的只有6岁。而前驱糖尿病患者数量更多。 糖尿病是一种令人讨厌的病,虽然肥胖会增加治病的可能性,但它更倾向于穷人。糖尿病的病因多由饮食和锻炼的不均衡引起。改善生活方式可以在一定程度上阻止糖尿病的发生,但胰岛素分泌和胰岛素利用的研究将更有助于糖尿病的治疗。从分子和生物化学水平上进行研究,弄清系统控制机制是目前所需的。

非损伤微测技术通过观察细胞代谢情况可以更好的研究糖尿病的发病机制。Beta 细胞分泌胰岛素的模式是吸收葡萄糖,改变氧耗,同时伴随ADP/ATP速率的变化及细胞去极化和Ca++内流。非损伤微测技术中葡萄糖电极和氧电极的应用将为胰岛素分泌模式的研究提供新的思路(A.J.h-Endocrinology and Metabolism)。目前有研究表明葡萄糖依赖的胰岛素分泌还跟骨骼肌运动有关(Diabetes)

非损伤微测技术在细胞、胰岛控制的胰岛素分泌的研究方面应用广泛。这些研究的结果对目前脉动式胰岛素分泌提出了质疑。研究中对beta细胞分泌途径进行一定的控制,并且对综合调控机制比如肠神经系统施加较多压力。

 

举例

 

葡萄糖刺激β细胞后,应用氧电极,可检测到氧暂时的波动(A.J.h-Endocrinology and Metabolism)

 

 

A.  电脑控制下纪录组织附近O2的流动情况。电极移动距离10μm,频率0.3Hz

B.   微电极检测卵黄囊胚胎的O2的流动情况。

C.  高糖小鼠晶胚对照组O2流的比较。

 

参考文献:

 

1) Li R., Chase, M., Jung, S.K., Smith, P.J.S., and Loeken, M.R. 2005. Hypoxic stress in diabetic pregnancy contributes to defective embryo gene expression and defective development by inducing oxidative stress. American Journal of Physiology-Endocrinology and Metabolism, 289: E591-E599. 

2) MacLellan, J. D., Gowing, A., Gerrits, M., Smith, P.J.S., Sivitz, W., Wheeler, M. B., and Harper, M. E. 2005. Physiological increases in uncoupling protein 3 augment fatty acid oxidation adn decrease reactive oxygen species production without unoupling muscle cells. Diabetes, 54:2343-2350.

3) Katzman, S.M., Messerli, M.A., Barry, D.T, Grossman, A., Harel,T., Wikstrom, J.D., Corkey, B.E., Smith, P.J.S., Shirihai,O.S. 2004. Mitochondrial metabolism reveals a functional architecture in intact islets of Langerhans from normal and diabetic Psammomys obesus. American Journal of Physiology-Endocrinology and Metabolism, 287: E1090-E1099.

4) Wikstrom, J.D., Katzman, S.M., and Shirihai, O.S. 2004. Functional heterogeneity of mitochondria in an individual beta cell. Diabetologia, 47: A26.

5) Wikstrom, J.D., Katzman, S.M., and Shirihai, O.S. 2002. Functional diversity of mitochondria within single pancreatic islet cells demonstrates patterns unique to healthy and diabetic islets. Biological Bulletin, 208: 268.

6) Jung, S.-K., Trimarchi, J.R., Sanger, R.H. and Smith, P.J.S. 2001. Development and application of a self-referencing glucose microsensor for the measurement of glucose consumption by pancreatic beta cells. Analytical Chemistry, 73(15): 3759-3767.

7) Jung, S.-K., Hammar, K. and Smith, P.J.S. 2000. Development of self-referencing oxygen microsensor and its application to HIT cells. Biological Bulletin, 199(2): 197-198. 

8) Porterfield, D.M., Corkey, R.F., Sanger, R.H., Tornheim, K., Smith, P.J.S. and Corkey, B.E. 2000. Oxygen consumption oscillates in single clonal pancreatic beta -cells (HIT). Diabetes, 49: 1511-1516.