Nisi A Valentina, Arnold Myrtha M L, Blonde Ginger D, Schier Lindsey A, Sanchez-Watts Graciela, Watts Alan G, Langhans Wolfgang, Spector Alan C
Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida, United States.
Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
Am J Physiol Endocrinol Metab. 2025 Aug 1;329(2):E210-E225. doi: 10.1152/ajpendo.00460.2024. Epub 2025 Jun 25.
To help resolve the characteristics of orally stimulated endocrine responses to sugar, we developed a novel rat preparation with surgically implanted intraoral (IO) and intragastric (IG) cannulas for stimulus delivery, along with jugular vein catheters for blood sampling, and tested the effects of 1-min and 10-min IO versus IG infusions (1 mL/min) of 1.0 M glucose on plasma levels of insulin, glucose-dependent insulinotropic polypeptide (GIP), and glucose. Oral glucose delivery (1 min and 10 mins) caused a greater ( ≤ 0.05) early rise (1 min) in insulin levels than gastric glucose delivery, also reflected in the 3-min area under the curve (AUC). The 10-min, but not the 1-min, IO glucose infusion also caused a greater ( ≤ 0.05) increase in GIP levels than the IG infusions, as evidenced by the 3-min AUC. Oral delivery of 1.0 M fructose produced marginally (but significantly) higher insulin and GIP levels than gastric fructose delivery, although the difference appeared much smaller than that observed for isomolar glucose, suggesting some degree of chemospecificity and the involvement of a taste type 1 receptor-independent mechanism. Our triple cannulation/catheterization rat preparation is well suited to assess endocrine responses to oral stimulation. By comparing the effects of stimulus infusion into the oral cavity (oral + postoral stimulation) with the stimulus infusion directly into the stomach (only postoral stimulation), we confirmed the primacy of glucose to orally trigger an increase in circulating insulin while controlling for changes in plasma glucose. This approach offers promise for reliably characterizing orally stimulated endocrine responses in rats and potentially in other animal models as well. We describe an innovative preparation that can effectively characterize orally stimulated endocrine responses during ongoing ingestion in rats. We found that glucose orally triggered an early rise in not only plasma insulin-which in some circumstances was present even as glycemia increased-but also glucose-dependent insulinotropic polypeptide, albeit more weakly. These endocrine responses to orally delivered fructose were weak or nonexistent, confirming the primacy of glucose as the key monosaccharide stimulus.
为了帮助解析口服刺激对糖的内分泌反应特征，我们开发了一种新型大鼠制备方法，通过手术植入口腔内（IO）和胃内（IG）插管用于刺激传递，同时植入颈静脉导管用于采血，并测试了以1 mL/分钟的速度向口腔内和胃内输注1.0 M葡萄糖1分钟和10分钟对血浆胰岛素、葡萄糖依赖性促胰岛素多肽（GIP）和葡萄糖水平的影响。与胃内输注葡萄糖相比，口服葡萄糖（1分钟和10分钟）导致胰岛素水平在早期（1分钟）有更大幅度（≤0.05）的升高，这也反映在3分钟曲线下面积（AUC）上。10分钟而非1分钟的口腔内葡萄糖输注也导致GIP水平比胃内输注有更大幅度（≤0.05）的升高，3分钟AUC证明了这一点。口服1.0 M果糖产生的胰岛素和GIP水平略高于（但显著高于）胃内输注果糖，尽管这种差异似乎比等摩尔葡萄糖观察到的差异小得多，这表明存在一定程度的化学特异性以及味觉1型受体非依赖性机制的参与。我们的三插管/导管插入大鼠制备方法非常适合评估对口服刺激的内分泌反应。通过比较向口腔内输注刺激物（口腔 + 口腔后刺激）与直接向胃内输注刺激物（仅口腔后刺激）的效果，我们在控制血浆葡萄糖变化的同时，证实了葡萄糖在口服引发循环胰岛素增加方面的首要地位。这种方法有望可靠地表征大鼠以及潜在其他动物模型中口服刺激的内分泌反应。我们描述了一种创新的制备方法，它可以有效地表征大鼠在持续摄食过程中口服刺激的内分泌反应。我们发现口服葡萄糖不仅会引发血浆胰岛素的早期升高——在某些情况下，即使血糖升高时胰岛素也会升高——还会引发葡萄糖依赖性促胰岛素多肽的升高，尽管其作用较弱。这些对口服果糖的内分泌反应较弱或不存在，证实了葡萄糖作为关键单糖刺激的首要地位。
