Janssen Research & Development, Cardiovascular and Metabolism, 1400 McKean Rd., Spring House, PA, 19477, USA.
Cardiovascular and Metabolic Diseases, Crown Bioscience, Inc., 6 Beijing West Road, Taicang, Jiangsu Province, 215400, People's Republic of China.
Sci Rep. 2021 Jun 4;11(1):11866. doi: 10.1038/s41598-021-91027-3.
Meal ingestion elicits a variety of neuronal, physiological and hormonal responses that differ in healthy, obese or diabetic individuals. The mixed meal tolerance test (MMTT) is a well-established method to evaluate pancreatic β-cell reserve and glucose homeostasis in both preclinical and clinical research in response to calorically defined meal. Nonhuman primates (NHPs) are highly valuable for diabetic research as they can naturally develop type 2 diabetes mellitus (T2DM) in a way similar to the onset and progression of human T2DM. The purpose of this study was to investigate the reproducibility and effects of a MMTT containing acetaminophen on plasma glucose, insulin, C-peptide, incretin hormones, lipids, acetaminophen appearance (a surrogate marker for gastric emptying) in 16 conscious obese cynomolgus monkeys (Macaca fascicularis). Plasma insulin, C-peptide, TG, aGLP-1, tGIP, PYY and acetaminophen significantly increased after meal/acetaminophen administration. A subsequent study in 6 animals showed that the changes of plasma glucose, insulin, C-peptide, lipids and acetaminophen were reproducible. There were no significant differences in responses to the MMTT among the obese NHPs with (n = 11) or without (n = 5) hyperglycemia. Our results demonstrate that mixed meal administration induces significant secretion of several incretins which are critical for maintaining glucose homeostasis. In addition, the responses to the MMTTs are reproducible in NHPs, which is important when the MMTT is used for evaluating post-meal glucose homeostasis in research.
进食会引起各种神经元、生理和激素反应，这些反应在健康人、肥胖者或糖尿病患者中有所不同。混合餐耐量试验（MMTT）是一种成熟的方法，可用于评估临床前和临床研究中热量定义的膳食对胰腺β细胞储备和葡萄糖稳态的影响。非人类灵长类动物（NHPs）在糖尿病研究中非常有价值，因为它们可以自然地发展为 2 型糖尿病（T2DM），其方式类似于人类 T2DM 的发病和进展。本研究旨在研究含有对乙酰氨基酚的 MMTT 在 16 只清醒肥胖食蟹猴（Macaca fascicularis）中对血浆葡萄糖、胰岛素、C 肽、肠降血糖素激素、脂质、对乙酰氨基酚出现（胃排空的替代标志物）的重现性和影响。进食/对乙酰氨基酚给药后，血浆胰岛素、C 肽、TG、aGLP-1、tGIP、PYY 和对乙酰氨基酚明显增加。随后在 6 只动物中的研究表明，血浆葡萄糖、胰岛素、C 肽、脂质和对乙酰氨基酚的变化具有重现性。在伴有（n=11）或不伴有（n=5）高血糖的肥胖 NHP 中，MMTT 的反应没有显著差异。我们的结果表明，混合餐给药会引起几种肠降血糖素的显著分泌，这些激素对维持葡萄糖稳态至关重要。此外，MMTT 在 NHP 中的反应具有重现性，这在使用 MMTT 评估研究中餐后葡萄糖稳态时非常重要。
