Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston, MA 02114, USA.
Trends Endocrinol Metab. 2010 Feb;21(2):59-67. doi: 10.1016/j.tem.2009.11.007. Epub 2009 Dec 16.
GLP-1 (9-36)amide is the cleavage product of GLP-1(7-36) amide, formed by the action of diaminopeptidyl peptidase-4 (Dpp4), and is the major circulating form in plasma. Whereas GLP-1(7-36)amide stimulates glucose-dependent insulin secretion, GLP-1(9-36)amide has only weak partial insulinotropic agonist activities on the GLP-1 receptor, but suppresses hepatic glucose production, exerts antioxidant cardioprotective actions and reduces oxidative stress in vasculature tissues. These insulin-like activities suggest a role for GLP-1 (9-36)amide in the modulation of mitochondrial functions by mechanisms independent of the GLP-1 receptor. In this paper, we discuss the current literature suggesting that GLP-1(9-36)amide is an active peptide with important insulin-like actions. These findings have implications in nutrient assimilation, energy homeostasis, obesity, and the use of Dpp4 inhibitors for the treatment of diabetes.
GLP-1(9-36)酰胺是 GLP-1(7-36)酰胺的裂解产物，由二肽基肽酶-4（Dpp4）作用形成，是血浆中的主要循环形式。虽然 GLP-1(7-36)酰胺刺激葡萄糖依赖性胰岛素分泌，但 GLP-1(9-36)酰胺对 GLP-1 受体仅具有较弱的部分胰岛素激动剂活性，但抑制肝葡萄糖产生，发挥抗氧化心脏保护作用，并减少血管组织中的氧化应激。这些胰岛素样作用表明 GLP-1(9-36)酰胺在通过独立于 GLP-1 受体的机制调节线粒体功能方面发挥作用。在本文中，我们讨论了目前的文献，这些文献表明 GLP-1(9-36)酰胺是一种具有重要胰岛素样作用的活性肽。这些发现对营养吸收、能量平衡、肥胖以及 Dpp4 抑制剂在糖尿病治疗中的应用具有重要意义。
