Gerich J E
Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
Baillieres Clin Endocrinol Metab. 1993 Jul;7(3):551-86. doi: 10.1016/s0950-351x(05)80207-1.
Maintenance of plasma glucose concentrations within a narrow range despite wide fluctuations in the demand (e.g. vigorous exercise) and supply (e.g. large carbohydrate meals) of glucose results from coordination of factors that regulate glucose release into and removal from the circulation. On a moment-to-moment basis these processes are controlled mainly by insulin and glucagon, whose secretion is reciprocally influenced by the plasma glucose concentration. In the resting postabsorptive state, release of glucose from the liver (equally via glycogenolysis and gluconeogenesis) is the key regulated process. Glycogenolysis depends on the relative activities of glycogen synthase and phosphorylase, the latter being the more important. The activities of fructose-1,6-diphosphatase, phosphoenolpyruvate carboxylkinase and pyruvate dehydrogenase regulate gluconeogenesis, whose main precursors are lactate, glutamine and alanine. In the postprandial state, suppression of liver glucose output and stimulation of skeletal muscle glucose uptake are the most important factors. Glucose disposal by insulin-sensitive tissues is regulated initially at the transport step and the mainly by glycogen synthase, phosphofructokinase and pyruvate dehydrogenase. Hormonally induced changes in intracellular fructose 2,6-bisphosphate concentrations play a key role in muscle glycolytic flux and both glycolytic and gluconeogenic flux in the liver. Under stressful conditions (e.g. hypoglycaemia, trauma, vigorous exercise), increased secretion of other hormones such as adrenaline, cortisol and growth hormone, and increased activity of the sympathetic nervous system, come into play; their actions to increase hepatic glucose output and to suppress tissue glucose uptake are partly mediated by increases in tissue fatty acid oxidation. In diabetes, the most common disorder of glucose homeostasis, fasting hyperglycaemia, results primarily from excessive release of glucose by the liver due to increased gluconeogenesis; postprandial hyperglycaemia results from both impaired suppression of hepatic glucose release and impaired skeletal muscle glucose uptake. These abnormalities are usually due to the combination of impaired insulin secretion and tissue resistance to insulin, the causes of which remain to be determined.
尽管葡萄糖的需求（如剧烈运动）和供应（如大量碳水化合物餐）存在大幅波动，但血浆葡萄糖浓度仍能维持在狭窄范围内，这是由调节葡萄糖释放到循环系统以及从循环系统中清除的多种因素相互协调的结果。在每时每刻，这些过程主要受胰岛素和胰高血糖素的控制，它们的分泌受到血浆葡萄糖浓度的反向影响。在静息的吸收后状态下，肝脏释放葡萄糖（通过糖原分解和糖异生同等程度地进行）是关键的调节过程。糖原分解取决于糖原合酶和磷酸化酶的相对活性，后者更为重要。果糖 -1,6-二磷酸酶、磷酸烯醇式丙酮酸羧激酶和丙酮酸脱氢酶的活性调节糖异生，其主要前体是乳酸、谷氨酰胺和丙氨酸。在餐后状态下，抑制肝脏葡萄糖输出和刺激骨骼肌葡萄糖摄取是最重要的因素。胰岛素敏感组织对葡萄糖的处置最初在转运步骤进行调节，主要通过糖原合酶、磷酸果糖激酶和丙酮酸脱氢酶。激素诱导的细胞内果糖2,6-二磷酸浓度变化在肌肉糖酵解通量以及肝脏的糖酵解和糖异生通量中起关键作用。在应激条件下（如低血糖、创伤、剧烈运动），其他激素如肾上腺素、皮质醇和生长激素的分泌增加，以及交感神经系统活性增强开始发挥作用；它们增加肝脏葡萄糖输出和抑制组织葡萄糖摄取的作用部分是通过组织脂肪酸氧化增加介导的。在糖尿病（最常见的葡萄糖稳态紊乱）中，空腹高血糖主要是由于糖异生增加导致肝脏过度释放葡萄糖；餐后高血糖是由于肝脏葡萄糖释放抑制受损和骨骼肌葡萄糖摄取受损共同导致的。这些异常通常是由于胰岛素分泌受损和组织对胰岛素抵抗的共同作用，其原因仍有待确定。
