Rizzo Manfredi, Nikolic Dragana, Banach Maciej, Patti Angelo Maria, Montalto Giuseppe, Rizvi Ali A
Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine, Two Medical Park, Suite 502, Columbia, South Carolina, USA.
Curr Pharm Des. 2014;20(31):4953-60. doi: 10.2174/1381612819666131206102255.
Incretin peptides are a group of gastrointestinal hormones that play a prominent role in the regulation of glucose metabolism. Incretin-based therapies (IBTs) have recently emerged as an important treatment option for patients with type 2 diabetes mellitus (T2DM). These pharmaceutical agents may be specially well suited for patients who are overweight or obese with primarily post-meal glucose peaks, and in whom traditional first-line oral agents have failed to maintain adequate glycemic control. There are 2 classes of IBTs: the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide 1 (GLP-1) receptor agonists. The ultimate effect of both types of agents is to augment GLP-1 signaling, which results in enhanced glucose-dependent insulin secretion, inhibition of glucagon secretion and decreased appetite. This leads to improved regulation of glucose homeostasis accompanied by either no increase in body weight (with DPP-4 inhibitors) or a reduction (with GLP-1 receptor agonists). GLP-1 inhibits food intake and the increased GLP-1 response may contribute as a satiety signal. Although data regarding the effect of GLP-1 agonists and DPP-4 inhibitors on levels of peptides involved in the regulation of food intake in T2DM are few, an indirect effect of IBT on weight loss is possible (e.g. Exendin-4 induces adiponectin secretion in vitro). Results from animal models indicate reduction of food intake and body weight by GLP-1 agonists, but follow-up studies are required. A growing amount of evidence suggests that these peptides may also impact the cardiovascular system, including beneficial effects on myocardial cells, lipid profiles and blood pressure as well as reduced markers of systemic inflammation and improved endothelial dysfunction. The potential role of these agents in improving components of the metabolic syndrome and retardation of atherosclerosis needs to be fully elucidated. Although IBTs are currently recommended only for use in the early treatment of T2DM, the 'non-glycemic' actions of these drugs may have far reaching therapeutic implications. It is hoped that future studies will elucidate their potential strengths and weaknesses for use in various metabolic conditions.
肠促胰岛素肽是一类胃肠激素，在葡萄糖代谢调节中发挥着重要作用。基于肠促胰岛素的疗法（IBTs）最近已成为2型糖尿病（T2DM）患者的一种重要治疗选择。这些药物可能特别适合超重或肥胖且主要表现为餐后血糖峰值，而传统一线口服药物未能维持足够血糖控制的患者。有两类IBTs：二肽基肽酶-4（DPP-4）抑制剂和胰高血糖素样肽-1（GLP-1）受体激动剂。这两类药物的最终作用都是增强GLP-1信号传导，从而导致葡萄糖依赖性胰岛素分泌增加、胰高血糖素分泌受抑制以及食欲降低。这会改善葡萄糖稳态调节，同时体重不增加（使用DPP-4抑制剂时）或减轻（使用GLP-1受体激动剂时）。GLP-1抑制食物摄入，增加的GLP-1反应可能作为一种饱腹感信号起作用。尽管关于GLP-1激动剂和DPP-4抑制剂对T2DM患者食物摄入调节相关肽水平影响的数据很少，但IBT对体重减轻可能有间接作用（例如艾塞那肽在体外诱导脂联素分泌）。动物模型结果表明GLP-1激动剂可减少食物摄入和体重，但仍需后续研究。越来越多的证据表明，这些肽还可能影响心血管系统，包括对心肌细胞、血脂谱和血压产生有益作用，以及降低全身炎症标志物和改善内皮功能障碍。这些药物在改善代谢综合征成分和延缓动脉粥样硬化方面的潜在作用需要充分阐明。尽管目前仅推荐IBTs用于T2DM的早期治疗，但这些药物的“非血糖”作用可能具有深远的治疗意义。希望未来的研究能阐明它们在各种代谢状况下使用的潜在优缺点。
