Effect of berberine on expression of hepatocyte nuclear factor-4alpha in rats with fructose-induced insulin resistance.
The effects of berberine on the expression of hepatocyte nuclear factor-4alpha (HNF-4alpha) in liver of rats with fructose-induced insulin resistance and the molecular mechanism of berberine preventing insulin resistance were investigated. The experimental animals were divided into two groups of 16 animals each. The control group received a control routine diet containing 60% carbohydrate, and the study group a high-fructose diet containing 60% fructose as the sole source of carbohydrate. At the end of 6 weeks these were each subdivided into two groups. One was administered with berberine [187.5 mg/(kg x d) in 5 g/L carboxymethyl cellulose] by intragastric intubation and the other group was treated with a vehicle (5 g/L carboxymethyl cellulose). The rats were fed on the same dietary regimen for the next 4 weeks. After the experimental period of 10 weeks, plasma glucose, insulin and triglyceride levels were measured. HOMA insulin resistance index (HOMA-IR) was assayed. Immunohistochemistry, semiquantitative RT-PCR and western blot were used to detect the expression of HNF-4alpha in liver. Compared with control diet, fructose feeding induced hyperinsulinemia, HOMA-IR and increased triglyceride (all P<0.01). Berberine prevented the rise in plasma insulin (P<0.01), HOMA-IR (P<0.01) and triglyceride (P<0.05) in the fructose-fed rats. No change in plasma glucose was seen among these groups. The mRNA and protein expression of HNF-4alpha was decreased in the fructose-fed rats, but berberine could promote its expression. It was concluded that berberine could prevent fructose-induced insulin resistance in rats possibly by promoting the expression HNF-4alpha in liver.
Gao
Zhiqiang
Z
Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. hbgzq@yahoo.com.cn
Leng
Sanhua
S
Lu
Fuer
F
Xie
Meijuan
M
Xu
Lijun
L
Wang
Kaifu
K
D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology*; D051557:Hepatocyte Nuclear Factor 4 / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D051557:Hepatocyte Nuclear Factor 4; D007328:Insulin; D012333:RNA, Messenger; D014280:Triglycerides; D001599:Berberine; D005632:Fructose