Weyer C, Maggs D G, Young A A, Kolterman O G
Amylin Pharmaceuticals Inc, 9373 Towne Centre Drive, San Diego, CA 92121, USA.
Curr Pharm Des. 2001 Sep;7(14):1353-73. doi: 10.2174/1381612013397357.
Destruction and dysfunction of pancreatic beta-cells, resulting in absolute and relative insulin deficiency, represent key abnormalities in the pathogenesis of type 1 and type 2 diabetes, respectively. Following the discovery of amylin, a second beta-cell hormone that is co-secreted with insulin in response to nutrient stimuli, it was realized that diabetes represents a state of bihormonal beta cell deficiency and that lack of amylin action may contribute to abnormal glucose homeostasis. Experimental studies show that amylin acts as a neuroendocrine hormone that complements the effects of insulin in postprandial glucose regulation through several centrally mediated effects. These include a suppression of postprandial glucagon secretion and a vagus-mediated regulation of gastric emptying, thereby helping to control the influx of endogenous and exogenous glucose, respectively. In animal studies, amylin has also been shown to reduce food intake and body weight, consistent with an additional satiety effect. Pramlintide is a soluble, non-aggregating, injectable, synthetic analog of human amylin currently under development for the treatment of type 1 and insulin-using type 2 diabetes. Long-term clinical studies have consistently demonstrated that pre-prandial s.c. injections of pramlintide, in addition to the current insulin regimen, reduce HbA(1c) and body weight in type 1 and type 2 diabetic patients, without an increase in insulin use or in the event rate of severe hypoglycemia. The most commonly observed side effects were gastrointestinal-related, mainly mild nausea, which typically occurred upon initiation of treatment and resolved within days or weeks. Amylin replacement with pramlintide as an adjunct to insulin therapy is a novel physiological approach toward improved long-term glycemic and weight control in patients with type 1 and type 2 diabetes.
胰腺β细胞的破坏和功能障碍分别导致绝对和相对胰岛素缺乏，这是1型和2型糖尿病发病机制中的关键异常。在发现胰淀素（一种在营养刺激下与胰岛素共同分泌的第二种β细胞激素）之后，人们认识到糖尿病代表双激素β细胞缺乏状态，并且缺乏胰淀素作用可能导致葡萄糖稳态异常。实验研究表明，胰淀素作为一种神经内分泌激素，通过几种中枢介导的作用补充胰岛素在餐后血糖调节中的作用。这些作用包括抑制餐后胰高血糖素分泌和迷走神经介导的胃排空调节，从而分别有助于控制内源性和外源性葡萄糖的流入。在动物研究中，胰淀素还被证明可以减少食物摄入量和体重，这与额外的饱腹感作用一致。普兰林肽是一种可溶性、非聚集性、可注射的人胰淀素合成类似物，目前正在开发用于治疗1型糖尿病和使用胰岛素的2型糖尿病。长期临床研究一致表明，除了当前的胰岛素治疗方案外，餐前皮下注射普兰林肽可降低1型和2型糖尿病患者的糖化血红蛋白（HbA₁c）水平和体重，而不会增加胰岛素使用量或严重低血糖事件发生率。最常见的副作用与胃肠道有关，主要是轻度恶心，通常在治疗开始时出现，并在数天或数周内缓解。用普兰林肽替代胰淀素作为胰岛素治疗的辅助手段，是一种改善1型和2型糖尿病患者长期血糖和体重控制的新型生理学方法。
