Graduate School of Agriculture, Hokkaido University, Kita-9, Nishi-9, Kita-ku, Sapporo060-8589, Japan.
Department of Food Science and Human Nutrition, Fuji Women's University, Ishikari061-3204, Japan.
Br J Nutr. 2021 Aug 28;126(4):518-530. doi: 10.1017/S000711452000433X. Epub 2020 Nov 4.
Glucagon-like peptide-1 (GLP-1) is postprandially secreted from enteroendocrine L-cells and enhances insulin secretion. Currently, it is still controversial whether postprandial GLP-1 responses are altered in obesity and diabetes. To address the issue and to find out possible factors related, we compared postprandial GLP-1 responses in normal rats and in diabetic rats chronically fed an obesogenic diet. Male Wistar rats and diabetic Goto-Kakizaki (GK) rats were fed either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose) diet for 26 weeks. Meal tolerance tests were performed for monitoring postprandial responses after a liquid diet administration (62·76 kJ/kg body weight) every 4 or 8 weeks. Postprandial glucose, GLP-1 and insulin responses in Wistar rats fed the HFS diet (WH) were higher than Wistar rats fed the control diet (WC). Although GK rats fed the HFS diet (GH) had higher glycaemic responses than GK rats fed the control diet (GC), these groups had similar postprandial GLP-1 and insulin responses throughout the study. Jejunal and ileal GLP-1 contents were increased by the HFS diet only in Wistar rats. Furthermore, mRNA expression levels of fatty acid receptors (Ffar1) in the jejunum were mildly (P = 0·053) increased by the HFS diet in Wistar rats, but not in GK rats. These results demonstrate that postprandial GLP-1 responses are enhanced under an obesogenic status in normal rats, but not in diabetic rats. Failure of adaptive enhancement of GLP-1 response in GK rats could be partly responsible for the development of glucose intolerance.
胰高血糖素样肽-1（GLP-1）是肠内分泌 L 细胞餐后分泌的，能增强胰岛素分泌。目前，肥胖和糖尿病患者餐后 GLP-1 反应是否改变仍存在争议。为了解决这个问题并找出可能相关的因素，我们比较了正常大鼠和长期喂食致肥胖饮食的糖尿病大鼠的餐后 GLP-1 反应。雄性 Wistar 大鼠和糖尿病 Goto-Kakizaki（GK）大鼠分别喂食对照饮食或高脂肪/高蔗糖（HFS，30%脂肪和 40%蔗糖）饮食 26 周。每隔 4 或 8 周进行一次液体饮食（62.76 kJ/kg 体重）管理后的耐餐试验，以监测餐后反应。HFS 饮食喂养的 Wistar 大鼠（WH）的餐后血糖、GLP-1 和胰岛素反应高于对照饮食喂养的 Wistar 大鼠（WC）。尽管 HFS 饮食喂养的 GK 大鼠（GH）的血糖反应高于对照饮食喂养的 GK 大鼠（GC），但在整个研究过程中，这两组的餐后 GLP-1 和胰岛素反应相似。只有 Wistar 大鼠的 HFS 饮食增加了空肠和回肠 GLP-1 含量。此外，Wistar 大鼠空肠脂肪酸受体（Ffar1）的 mRNA 表达水平也被 HFS 饮食轻度（P = 0.053）增加，但 GK 大鼠则没有。这些结果表明，正常大鼠在致肥胖状态下餐后 GLP-1 反应增强，但糖尿病大鼠则不然。GK 大鼠 GLP-1 反应适应性增强的失败可能是其葡萄糖耐量受损的部分原因。
