Antinozzi P A, Berman H K, O'Doherty R M, Newgard C B
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Annu Rev Nutr. 1999;19:511-44. doi: 10.1146/annurev.nutr.19.1.511.
Fuel homeostasis in mammals is accomplished by the interplay between tissues and organs with distinct metabolic roles. These regulatory mechanisms are disrupted in obesity and diabetes, leading to a renewed emphasis on discovery of molecular and pharmacologic methods for reversing metabolic disorders. In this chapter, we review the use of recombinant adenoviral vectors as tools for delivering metabolic regulatory genes to cells in culture and to tissues of intact animals. Included are studies on the use of these vectors for gaining insights into the biochemical mechanisms that regulate glucose-stimulated insulin secretion from pancreatic islet beta-cells. We also highlight their use for understanding the function of newly discovered genes that regulate glycogen metabolism in liver and other tissues, and for evaluating "candidate" genes such as glucose-6-phosphatase, which may contribute to development of metabolic dysfunction in pancreatic islets and liver. Finally, we discuss the use of adenoviral and related vectors for causing chronic increases in the levels of circulating hormones. These examples serve to highlight the power of viral gene transfer vectors as tools for understanding metabolic regulatory mechanisms.
哺乳动物的能量稳态是通过具有不同代谢作用的组织和器官之间的相互作用来实现的。这些调节机制在肥胖和糖尿病中会受到破坏，这使得人们重新重视发现逆转代谢紊乱的分子和药理学方法。在本章中，我们综述了重组腺病毒载体作为工具，将代谢调节基因传递到培养细胞和完整动物组织中的应用。其中包括利用这些载体深入了解调节胰岛β细胞葡萄糖刺激胰岛素分泌的生化机制的研究。我们还强调了它们在理解肝脏和其他组织中调节糖原代谢的新发现基因的功能，以及评估可能导致胰岛和肝脏代谢功能障碍的“候选”基因（如葡萄糖-6-磷酸酶）方面的应用。最后，我们讨论了使用腺病毒及相关载体使循环激素水平长期升高的情况。这些例子凸显了病毒基因转移载体作为理解代谢调节机制工具的强大作用。
