Goldsmith Felicia, Keenan Michael J, Raggio Anne M, Ye Xin, Hao Zheng, Durham Holiday, Geaghan James, Jia Weiping, Martin Roy J, Ye Jianping
Louisiana State University Agricultural Center, Baton Rouge, Louisiana 70803, United States of America.
Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, United States of America.
PLoS One. 2015 May 4;10(5):e0126177. doi: 10.1371/journal.pone.0126177. eCollection 2015.
Sitagliptin (SG) increases serum GLP-1 (Glucagon-like peptide-1) through inhibition of the hormone degradation. Resistant starch (RS) induces GLP-1 expression by stimulating L-cells in the intestine. Sitagliptin and resistant starch may have a synergistic interaction in the induction of GLP-1. This possibility was tested in current study in a mouse model of type 2 diabetes. Hyperglycemia was induced in the diet-induced obese mice by a signal injection of streptozotocin (STZ). Sitagliptin (0.4g/100g diet) was tested in the mice (n = 55) with dietary RS (HAM-RS2) at three dosages (0, 15, or 28g/100g diet). Energy and glucose metabolism were monitored in the evaluation of synergistic activity, and GLP-1 activity was determined in the GLP-1 receptor knockout (KO) mice. In the wild type mice, body weight and adiposity were reduced by sitagliptin, which was enhanced by RS (28g). Serum GLP-1 was induced and energy expenditure was enhanced by sitagliptin. Fasting glucose, insulin, and leptin levels were decreased by sitagliptin. The sitagliptin effects were lost in the KO mice (n = 25) although induction of serum GLP-1 by sitagliptin was even stronger in KO mice. The data suggests that sitagliptin is able to reduce adiposity and insulin resistance through induction of energy expenditure. The effect of sitagliptin is partially enhanced by RS. GLP-1 receptor may regulate serum GLP-1 by facilitating the hormone clearance.
西他列汀（SG）通过抑制激素降解来提高血清胰高血糖素样肽-1（GLP-1）水平。抗性淀粉（RS）通过刺激肠道中的L细胞诱导GLP-1表达。西他列汀和抗性淀粉在诱导GLP-1方面可能存在协同相互作用。在当前的一项2型糖尿病小鼠模型研究中对这种可能性进行了测试。通过单次注射链脲佐菌素（STZ）在饮食诱导的肥胖小鼠中诱发高血糖。在添加了三种剂量（0、15或28g/100g饮食）的膳食抗性淀粉（HAM-RS2）的小鼠（n = 55）中测试了西他列汀（0.4g/100g饮食）。在评估协同活性时监测能量和葡萄糖代谢，并在GLP-1受体敲除（KO）小鼠中测定GLP-1活性。在野生型小鼠中，西他列汀可减轻体重和肥胖，而抗性淀粉（28g）可增强这种作用。西他列汀可诱导血清GLP-1并增加能量消耗。西他列汀可降低空腹血糖、胰岛素和瘦素水平。尽管西他列汀诱导血清GLP-1的作用在KO小鼠中更强，但在KO小鼠（n = 25）中却未观察到西他列汀的上述作用。数据表明，西他列汀能够通过诱导能量消耗来减轻肥胖和胰岛素抵抗。抗性淀粉可部分增强西他列汀的作用。GLP-1受体可能通过促进激素清除来调节血清GLP-1水平。
