School of Medicine, University of Auckland, Auckland, New Zealand.
Expert Opin Investig Drugs. 2021 Jul;30(7):737-747. doi: 10.1080/13543784.2021.1931118. Epub 2021 May 30.
Post-pancreatitis diabetes mellitus is one of the most common types of secondary diabetes. The pharmaceutical armamentarium in the field of diabetology can be broadened if the design of novel drugs is informed by pathogenetic insights from studies on post-pancreatitis diabetes mellitus. The article provides an overview of preclinical and clinical studies of compounds selectively antagonizing the gastric inhibitory peptide receptor, simultaneously stimulating both the glucagon-like peptide-1 and glucagon receptors, and activating ketogenesis. The current pharmacotherapy for post-pancreatitis diabetes mellitus is relatively ineffective. This type of diabetes represents a unique platform for rigorous, efficient, and practical search for glucose-lowering therapeutic candidates. Various methods of gastric inhibitory peptide receptor (expressed in the pancreas) antagonism have undergone extensive preclinical testing in diabetes, with promising compounds being trialed in man. Molecular mimicry with oxyntomodulin ─ an extra-pancreatic hormone homologous with pancreatic hormone glucagon and involved in the regulation of exocrine pancreatic function ─ could be harnessed. The emerging findings of a salutary effect of ketosis mimetics in people with prediabetes set the stage for a novel approach to preventing diabetes.
胰腺炎后糖尿病是最常见的继发性糖尿病之一。如果新型药物的设计能够从胰腺炎后糖尿病的研究中获得发病机制方面的深入了解，那么糖尿病学领域的药物种类将会得到扩展。本文综述了选择性拮抗胃抑制肽受体、同时刺激胰高血糖素样肽-1 和胰高血糖素受体以及激活酮体生成的化合物的临床前和临床研究。目前对胰腺炎后糖尿病的药物治疗效果相对不理想。这种类型的糖尿病代表了一个独特的平台，可以进行严格、高效和实用的降糖治疗候选药物的探索。已经在糖尿病中对胃抑制肽受体（在胰腺中表达）的各种拮抗方法进行了广泛的临床前测试，具有前景的化合物已在人类中进行试验。与胰高血糖素同源的、参与外分泌胰腺功能调节的胃肠激素——胰泌素的分子模拟可以被利用。在糖尿病前期人群中酮体类似物有益作用的新发现为预防糖尿病提供了一种新方法。
