Zhenqing recipe improves glucose metabolism and insulin sensitivity by repressing hepatic FOXO1 in type 2 diabetic rats.
Forkhead box O1 (FOXO1) plays an important role in glucose metabolism at the gene transcription level. Increased FOXO1 activity results in hyperglycemia by promoting the expression of gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), and inhibiting glucokinase (GK). This study evaluates the effect of Zhenqing Recipe (ZQR), a Chinese herbal medicine, on hyperglycemia and its molecular mechanisms. Type 2 diabetic rats, developed by high-fat diet combined with low-dose STZ injections, were randomly divided into untreated diabetic, ZQR and metformin group. Normal rats served as control. After an eight-week treatment, fasting blood glucose was significantly decreased and insulin sensitivity index was obviously increased in the ZQR group. ZQR also improved the oral glucose tolerance. Compared with the control group, the mRNA levels of PEPCK and G6Pase were significantly elevated, while GK mRNA expression was decreased in the liver of untreated diabetic rats. ZQR significantly reduced the mRNA levels of PEPCK and G6Pase, and increased GK mRNA expression. The hepatic mRNA and protein expression of FOXO1 in the untreated diabetic group was markedly increased compared to controls. The administration of ZQR significantly decreased the mRNA and protein levels of hepatic FOXO1. The data suggest that ZQR improves glucose metabolism and insulin sensitivity, which is accompanied with regulating mRNA expression of GK and gluconeogenic genes. This anti-diabetic effect of ZQR is due to its ability to repress hepatic FOXO1 at the mRNA and protein level.
Department of Traditional Chinese Medicine and Endocrinology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Wenfan
W
Huang
Jie
J
Yu
Xuming
X
Jia
Liang
L
Xiong
Ningxu
N
Li
Xiuying
X
Wen
D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D000071161:Forkhead Box Protein O1
D001786:Blood Glucose; D017931:DNA Primers; D004365:Drugs, Chinese Herbal; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; C550196:zhenqing; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1