Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
Mol Cell Endocrinol. 2020 Mar 1;503:110696. doi: 10.1016/j.mce.2019.110696. Epub 2019 Dec 28.
We aim to investigate the expression of the glucagon receptor (GCGR) in human adipose tissue, and the impact of glucagon in glucose uptake and lipolysis in human adipocytes. GCGR gene expression in human subcutaneous and visceral adipose tissue was demonstrated, albeit at low levels and with an inter-individual variation. Furthermore, GCGR expression was not significantly different between subjects with T2D and matched controls, and we found no significant association with BMI. Glucagon only at a supra-physiological concentration (10-100 nM) significantly increased basal and insulin-stimulated glucose uptake by up to 1.5-fold. Also, glucagon (0.01 and 1 nM) dose-dependently increased basal and isoproterenol-stimulated lipolysis up to 3.7- and 1.7-fold, respectively, compared to control. In addition, glucagon did not change insulin sensitivity to stimulate glucose uptake or inhibit lipolysis. In conclusion, we show that the GCGR gene is expressed at low levels in human adipose tissue, and glucagon at high concentrations can increase both glucose uptake and lipolysis in human adipocytes. Taken together, our data suggest that glucagon at physiological levels has minor direct effects on the regulation of adipocyte metabolism, but does not antagonize the insulin effect to stimulate glucose uptake and inhibit lipolysis in human adipocytes.
我们旨在研究胰高血糖素受体（GCGR）在人体脂肪组织中的表达，以及胰高血糖素对人体脂肪细胞葡萄糖摄取和脂肪分解的影响。尽管 GCGR 基因在人体皮下和内脏脂肪组织中的表达水平较低且个体间存在差异，但我们已经证实了其表达。此外，2 型糖尿病患者和匹配对照者之间的 GCGR 表达并无明显差异，且我们发现其与 BMI 之间无显著相关性。只有在超生理浓度（10-100 nM）下，胰高血糖素才会显著增加基础和胰岛素刺激的葡萄糖摄取，最高可达 1.5 倍。此外，与对照组相比，胰高血糖素（0.01 和 1 nM）可剂量依赖性地分别增加基础和异丙肾上腺素刺激的脂肪分解，最高可达 3.7 倍和 1.7 倍。此外，胰高血糖素并未改变胰岛素敏感性，以刺激葡萄糖摄取或抑制脂肪分解。总之，我们表明 GCGR 基因在人体脂肪组织中低水平表达，而高浓度的胰高血糖素可增加人体脂肪细胞的葡萄糖摄取和脂肪分解。综上所述，我们的数据表明，生理水平的胰高血糖素对脂肪细胞代谢的调节仅有轻微的直接影响，但不会拮抗胰岛素刺激葡萄糖摄取和抑制脂肪分解的作用。
