Publications (2)1.95 Total impact
Article: Establishment of liver specific glucokinase gene knockout mice: a new animal model for screening anti-diabetic drugs.[show abstract] [hide abstract]
ABSTRACT: To characterize the liver-specific role of glucokinase in maintaining glucose homeostasis and to create an animal model for diabetes. We performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP gene targeting strategy. First, two directly repeated loxP sequences were inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To achieve this, linearized targeting vector was electroporated into ES cells. Then G418- and Gancyclovir-double-resistant clones were picked and screened by PCR analysis and the positives identified by PCR were confirmed by Southern blot. A targeted clone was selected for microinjection into C57BL/6J blastocysts and implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice with mice containing a conditional gk allele, we obtained mice with liver-specific glucokinase gene knockout. Among 161 double resistant clones 4 were positive to PCR and Southern blot and only one was used for further experiments. Eventually we generated the liver specific glucokinase knockout mice. These mice showed increased glucose level with age and at the age of 6 weeks fasting blood glucose level was significantly higher than control and they also displayed impaired glucose tolerance. Our studies indicate that hepatic glucokinase plays an important role in glucose homeostasis and its deficiencies contribute to the development of diabetes. The liver glucokinase knockout mouse is an ideal animal model for MODY2, and it also can be applied for screening anti-diabetic drugs.Acta Pharmacologica Sinica 01/2005; 25(12):1659-65. · 1.95 Impact Factor
Article: [Experimental study on the pharmacology of 999 ganmaoling, a compound recipe of Chinese and Western materia medica].[show abstract] [hide abstract]
ABSTRACT: To study the pharmacologic characteristics in synergism and complementation of 999 Ganmaoling (GML), a compound recipe composed of Chinese and Western materia medica (CMM & WMM), as well as its theoretical basis of matching of Chinese and Western materia medica. The torsion response induced by glacial acetic acid in mice, toe swelling induced by carrageenanin rats, delayed hypersensitive response in mice and fever induced by endotoxin in rats and rabbits were used to comparatively study the actions of CMM & WMM in GML. The effect of CMM in antagonizing liver damage caused by WD (acetaminophen) in mice was also studied. RT-PCR method was used to analyze the expression of related cytokines. GML showed a significant antipyretic and analgesic effect, it could inhibit the carrageenan induced inflammation, antagonize the endotoxin induced fever, and promote the amount for expression of cytokines in rats' splenic tissue with pneumococci infection to some extent. The CMM in GML showed certain protective effect on acetaminophen induced liver damage. GML has a potent antipyretic, analgesic and anti-inflammatory effects, CMM & WMM in GML showed markedly synergism and complementation, and CMM in it has liver protective effect.Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 08/2004; 24(8):726-30.