Kitamura Tadahiro, Kobayashi Masaki
Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512 Japan.
Diabetol Int. 2024 Mar 27;15(3):362-369. doi: 10.1007/s13340-024-00704-x. eCollection 2024 Jul.
Glucagon has many functions: it promotes glucose production, fatty acid oxidation, thermogenesis, energy consumption, lipolysis, and myocardial contraction, and suppresses lipogenesis, appetite, and gastrointestinal motility. Which of these functions are physiological and which are pharmacological is not fully understood. Although the Mercodia sandwich ELISA provides significantly higher specificity of glucagon measurement than does conventional competitive RIA, it cannot provide accurate plasma glucagon values in the presence of elevated cross-reacting plasma glicentin. This occurs in patients post-pancreatectomy or bariatric surgery and in around 30% of outpatients suspected for glucose intolerance who have not had surgery. Thus, our newly developed sandwich ELISA with higher specificity and higher sensitivity than the Mercodia sandwich ELISA is needed for accurate measurements of plasma glucagon in diabetic patients. It is expected that the new sandwich ELISA will contribute to personalized medicine for diabetes by its use in clinical tests to accurately diagnose the conditions of diabetic patients in order to design better individual treatment strategies. Meanwhile, clinical trials are being conducted worldwide to apply glucagon/GLP-1 receptor dual agonists and glucagon/GLP-1/GIP receptor triagonists to the treatment of obesity, fatty liver, and diabetes. Most clinical trials have shown that both types of drugs have stronger effects on weight reduction, improving fatty liver, and glucose tolerance than do the single GLP-1 receptor agonists. Glucagon is expected to be used as a new diagnostic marker and in a new therapeutic strategy based on a true understanding of its physiological and pharmacological functions.
它促进葡萄糖生成、脂肪酸氧化、产热、能量消耗、脂肪分解和心肌收缩，并抑制脂肪生成、食欲和胃肠蠕动。这些功能中哪些是生理性的，哪些是药理学性的，目前尚未完全明确。尽管Mercodia夹心酶联免疫吸附测定法（ELISA）在测量胰高血糖素时比传统的竞争性放射免疫分析（RIA）具有更高的特异性，但在存在交叉反应性血浆肠高血糖素升高的情况下，它无法提供准确的血浆胰高血糖素值。这在胰腺切除术后或减肥手术后的患者中以及约30%未接受手术但疑似糖耐量异常的门诊患者中会出现。因此，需要一种比Mercodia夹心ELISA具有更高特异性和更高灵敏度的新开发的夹心ELISA，以准确测量糖尿病患者的血浆胰高血糖素。预计新的夹心ELISA将通过用于临床试验以准确诊断糖尿病患者的病情，从而设计更好的个体化治疗策略，为糖尿病的个性化医疗做出贡献。与此同时，全球正在进行临床试验，以将胰高血糖素/胰高血糖素样肽-1（GLP-1）受体双重激动剂和胰高血糖素/GLP-1/葡萄糖依赖性促胰岛素多肽（GIP）受体三重激动剂应用于肥胖、脂肪肝和糖尿病的治疗。大多数临床试验表明，这两种药物在减轻体重、改善脂肪肝和糖耐量方面比单一的GLP-1受体激动剂具有更强的作用。基于对其生理和药理功能的真正理解，胰高血糖素有望用作一种新的诊断标志物并用于一种新的治疗策略。
