The regulatory peptide 26RFa (QRFP) is involved in the control of glucose homeostasis at the periphery by acting as an incretin, and in the brain by mediating the central antihyperglycemic effect of insulin, indicating the occurrence of a close relationship between 26RFa and insulin in the regulation of glucose metabolism. Here, we investigated the physiological interactions between 26RFa and insulin in two complementary models i.e. a model of obese/hyperglycemic mice deficient for 26RFa and a model of diabetic mice deficient for insulin. For this, transgenic 26RFa-deficient mice were made obese and chronically hyperglycemic by a 3-month high fat diet (HFD) and second group of mice was made diabetic by destruction of the β cells of the pancreatic islets using a single injection of streptozotocin. Our data reveal that 26RFa deficiency does not impact significantly the “glycemic” phenotype of the HFD mice. The pancreatic islets, liver, white adipose tissue masses are not altered by the lack of 26RFa production but the brown adipose tissue (BAT) weight is significantly increased in these animals. In diabetic insulin-deficient mice, the injection of 26RFa does not exhibit any beneficial effect on the impaired glucose homeostasis characterizing this model. Finally, we show that streptozotocin diabetic mice display lowered plasma 26RFa levels as compared to untreated mice, whereas the expression of the peptide in the duodenum is not affected.

Taken together, the present results indicate that dysregulation of glucose homeostasis in obese/hyperglycemic mice is not aggravated by the absence of 26RFa that may be compensated by the increase of BAT mass. In diabetic insulin-deficient mice, the antihypergycemic effect of 26RFa is totally blunted probably as a result of the impaired insulin production characterizing this model, avoiding therefore the action of the peptide.

调节肽 26RFa (QRFP) 通过充当肠降血糖素参与外周葡萄糖稳态的控制，并通过介导胰岛素的中枢降糖作用参与脑内葡萄糖稳态的控制，表明 26RFa 与胰岛素之间存在密切关系葡萄糖代谢的调节。在这里，我们在两个互补模型中研究了 26RFa 和胰岛素之间的生理相互作用，即缺乏 26RFa 的肥胖/高血糖小鼠模型和缺乏胰岛素的糖尿病小鼠模型。为此，转基因 26RFa 缺陷小鼠通过 3 个月的高脂肪饮食 (HFD) 变得肥胖和长期高血糖，第二组小鼠通过单次注射链脲佐菌素破坏胰岛的 β 细胞而患上糖尿病。我们的数据显示 26RFa 缺乏不会显着影响 HFD 小鼠的“血糖”表型。胰岛、肝脏、白色脂肪组织块不会因缺乏 26RFa 产生而改变，但这些动物的棕色脂肪组织 (BAT) 重量显着增加。在糖尿病胰岛素缺乏小鼠中，注射 26RFa 对该模型的葡萄糖稳态受损没有任何有益影响。最后，我们表明与未治疗的小鼠相比，链脲佐菌素糖尿病小鼠显示出较低的血浆 26RFa 水平，而十二指肠中肽的表达不受影响。白色脂肪组织块不会因缺乏 26RFa 产生而改变，但这些动物的棕色脂肪组织 (BAT) 重量显着增加。在糖尿病胰岛素缺乏小鼠中，注射 26RFa 对该模型的葡萄糖稳态受损没有任何有益影响。最后，我们表明与未治疗的小鼠相比，链脲佐菌素糖尿病小鼠显示出较低的血浆 26RFa 水平，而十二指肠中肽的表达不受影响。白色脂肪组织块不会因缺乏 26RFa 产生而改变，但这些动物的棕色脂肪组织 (BAT) 重量显着增加。在糖尿病胰岛素缺乏小鼠中，注射 26RFa 对该模型的葡萄糖稳态受损没有任何有益影响。最后，我们表明与未治疗的小鼠相比，链脲佐菌素糖尿病小鼠显示出较低的血浆 26RFa 水平，而十二指肠中肽的表达不受影响。

综上所述，目前的结果表明，肥胖/高血糖小鼠的葡萄糖稳态失调不会因 26RFa 的缺失而加重，这可能会通过 BAT 质量的增加得到补偿。在糖尿病胰岛素缺乏小鼠中，26RFa 的抗高血糖作用完全减弱，可能是由于该模型特征性胰岛素产生受损，从而避免了肽的作用。