Raju Bharathi, Cryer Philip E
Division of Endocrinology, Metabolism and Lipid Research, Washington Univ. School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110, USA.
Am J Physiol Endocrinol Metab. 2005 Aug;289(2):E181-6. doi: 10.1152/ajpendo.00460.2004.
The prevalent view is that the postabsorptive plasma glucose concentration is maintained within the physiological range by the interplay of the glucose-lowering action of insulin and the glucose-raising action of glucagon. It is supported by a body of evidence derived from studies of suppression of glucagon (and insulin, among other effects) with somatostatin in animals and humans, immunoneutralization of glucagon, defective glucagon synthesis, diverse mutations, and absent or reduced glucagon receptors in animals and glucagon antagonists in cells, animals, and humans. Many of these studies are open to alternative interpretations, and some lead to seemingly contradictory conclusions. For example, immunoneutralization of glucagon lowered plasma glucose concentrations in rabbits, but administration of a glucagon antagonist did not lower plasma glucose concentrations in healthy humans. Evidence that the glycemic threshold for glucagon secretion, unlike that for insulin secretion, lies below the physiological range, and the finding that selective suppression of insulin secretion without stimulation of glucagon secretion raises fasting plasma glucose concentrations in humans underscore the primacy of insulin in the regulation of the postabsorptive plasma glucose concentration and challenge the prevalent view. The alternative view is that the postabsorptive plasma glucose concentration is maintained within the physiological range by insulin alone, specifically regulated increments and decrements in insulin, and the resulting decrements and increments in endogenous glucose production, respectively, and glucagon becomes relevant only when glucose levels drift below the physiological range. Although the balance of evidence suggests that glucagon is involved in the maintenance of euglycemia, more definitive evidence is needed, particularly in humans.
普遍观点认为，在胰岛素的降糖作用和胰高血糖素的升糖作用的相互影响下，吸收后血浆葡萄糖浓度维持在生理范围内。这一观点得到了一系列证据的支持，这些证据来自于对动物和人类使用生长抑素抑制胰高血糖素（以及胰岛素等其他效应）的研究、胰高血糖素的免疫中和、胰高血糖素合成缺陷、各种突变，以及动物体内胰高血糖素受体缺失或减少和细胞、动物及人类体内的胰高血糖素拮抗剂研究。这些研究中有许多存在其他解释的可能性，有些甚至得出了看似相互矛盾的结论。例如，胰高血糖素的免疫中和降低了兔子的血浆葡萄糖浓度，但给健康人注射胰高血糖素拮抗剂并没有降低血浆葡萄糖浓度。与胰岛素分泌不同，胰高血糖素分泌的血糖阈值低于生理范围的证据，以及选择性抑制胰岛素分泌而不刺激胰高血糖素分泌会提高人类空腹血浆葡萄糖浓度的发现，都强调了胰岛素在调节吸收后血浆葡萄糖浓度中的首要地位，并对普遍观点提出了挑战。另一种观点认为，吸收后血浆葡萄糖浓度仅靠胰岛素就能维持在生理范围内，具体来说是通过胰岛素的特定调节性增减以及内源性葡萄糖生成相应的减少和增加来实现的，只有当血糖水平降至生理范围以下时，胰高血糖素才会发挥作用。尽管现有证据的平衡表明胰高血糖素参与了血糖正常的维持，但仍需要更确凿的证据，尤其是在人类身上。
