Evaluation of insulin secretory capacity is essential to understand the pathophysiological condition of individuals with diabetes and to assess the efficacy of drugs used in treatment of the disease. The 1 mg intravenous glucagon stimulation test (GST) is widely used to evaluate residual β cell function; we previously reported that GST assessment of insulin secretory capacity is useful in assessing the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, recent reports indicate that pharmacological concentrations of glucagon stimulate insulin secretion through GLP-1 receptors, confounding the issue. The present studies were undertaken to reassess the reliability of the GST for evaluation of insulin secretory capacity under GLP-1RAs and dipeptidyl peptidase-4 inhibitors (DPP-4is). Our first study comprised individuals initiated with the treatment of GLP-1RAs evaluated by GSTs before and after treatment. Although the fasting C-peptide levels (CPR) were elevated after treatment, the induction of insulin secretion by glucagon was significantly reduced. Our second study compared glucagon-induced insulin secretion between DPP-4i users and non-users, assessed by GST after propensity score matching. While the fasting CPR were similar in the two investigations, glucagon-induced insulin secretion was significantly lower with DPP-4i use. These results suggest that GST might underestimate insulin secretory capacity under incretin-based therapy.

中文翻译：

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胰高血糖素刺激试验和胰岛素分泌能力在基于 Increlin 的糖尿病治疗临床评估中的作用


胰岛素分泌能力的评估对于了解糖尿病患者的病理生理状况和评估用于治疗该疾病的药物的疗效至关重要。1 mg 静脉胰高血糖素刺激试验 （GST） 广泛用于评估残余β细胞功能;我们之前报道过胰岛素分泌能力的 GST 评估有助于评估胰高血糖素样肽-1 受体激动剂 （GLP-1RAs） 的疗效。然而，最近的报告表明，胰高血糖素的药理浓度通过 GLP-1 受体刺激胰岛素分泌，使这个问题变得混乱。本研究旨在重新评估 GST 在 GLP-1RAs 和二肽基肽酶-4 抑制剂 （DPP-4is） 下评估胰岛素分泌能力的可靠性。我们的第一项研究包括开始接受 GLP-1RAs 治疗的个体，在治疗前后通过 GSTs 进行评估。虽然治疗后空腹 C 肽水平 （CPR） 升高，但胰高血糖素诱导胰岛素分泌的水平显著降低。我们的第二项研究比较了胰高血糖素诱导的 DPP-4i 使用者和非使用者之间的胰岛素分泌，在倾向评分匹配后通过 GST 进行评估。虽然两项调查中的空腹 CPR 相似，但使用 DPP-4i 时胰高血糖素诱导的胰岛素分泌显着降低。这些结果表明，在基于肠促胰岛素的治疗下，GST 可能低估了胰岛素分泌能力。