Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 811, Taiwan.
Department of Food Science, Rutgers University, New Brunswick, NJ 08901, USA.
Nutrients. 2021 Dec 19;13(12):4552. doi: 10.3390/nu13124552.
Impairment of adiponectin production and function is closely associated with insulin resistance and type 2 diabetes, which are linked to obesity. Studies in animal models have documented the anti-diabetic effects of tetrahydrocurcumin (THC). Although several possible mechanisms have been proposed, the contribution of adiponectin signaling on THC-mediated antihyperglycemic effects remains unknown. Here, we report that adiposity, steatosis, and hyperglycemia were potently attenuated in high-fat diet/streptozotocin-induced diabetic obese mice after they received 20 and 100 mg/kg THC for 14 weeks. THC upregulated UCP-1 in adipose tissue and elevated adiponectin levels in the circulation. THC upregulated the AdipoR1/R2-APPL1-mediated pathway in the liver and skeletal muscle, which contributes to improved insulin signaling, glucose utilization, and lipid metabolism. Furthermore, THC treatment significantly ( < 0.05) preserved islet mass, reduced apoptosis, and restored defective insulin expression in the pancreatic β-cells of diabetic obese mice, which was accompanied by an elevation of AdipoR1 and APPL1. These results demonstrated a potential mechanism underlying the beneficial effects of THC against hyperglycemia via the adiponectin-AdipoR pathway, and thus, may lead to a novel therapeutic use for type 2 diabetes.
脂联素的产生和功能受损与胰岛素抵抗和 2 型糖尿病密切相关，而这两者都与肥胖有关。动物模型研究已经证明了四氢姜黄素（THC）的抗糖尿病作用。尽管已经提出了几种可能的机制，但脂联素信号在 THC 介导的抗高血糖作用中的贡献尚不清楚。在这里，我们报告说，在高脂肪饮食/链脲佐菌素诱导的肥胖型糖尿病小鼠中，接受 20 和 100mg/kg THC 治疗 14 周后，肥胖、脂肪变性和高血糖得到了强有力的缓解。THC 上调了脂肪组织中的 UCP-1，并增加了循环中的脂联素水平。THC 上调了肝脏和骨骼肌中 AdipoR1/R2-APPL1 介导的途径，这有助于改善胰岛素信号、葡萄糖利用和脂质代谢。此外，THC 治疗显著（<0.05）保留了胰岛质量，减少了胰岛β细胞的凋亡，并恢复了糖尿病肥胖小鼠中胰岛素表达的缺陷，同时伴随着 AdipoR1 和 APPL1 的升高。这些结果表明，THC 通过脂联素- AdipoR 途径对抗高血糖的有益作用存在潜在的机制，因此，可能为 2 型糖尿病提供一种新的治疗用途。
