Alloxan 당뇨쥐에서 glucose 6 phosphatase siRNA 주입이 공복혈당에 미치는 영향

Abstract

Background : Synthetic short interfering RNAs(siRNAs) have been used successfully to silence gene expression in a variety of biological systems as well as vector-based siRNA expression systems. In this experiment, I evaluate the potential of RNAi as a therapy for diabetes by depression of G6Pase. Methods : siRNAs of G6Pase was constructed to siRNA-expressing plasmid DNA (siRNA-pDNA). siRNA-pDNA was injected to alloxan-diabetic mice through tail vein and monitored blood glucose level. The levels of G6Pase mRNA in liver of mice were measured by real time PCR and G6Pase activities were measured. Results : Postprandial blood glucose level was not changed between control and G6Pase siRNA-pDNA treated alloxan-diabetic mice. The 6hr fasting blood glucose levels of control and G6Pase siRNA-pDNA injected alloxan-diabetic mice were 210 ±23 mg/dL blood and 119±11 mg/dL blood respectively. The 12hr fasting blood glucose levels of control and G6Pase siRNA-pDNA injected alloxan-diabetic mice were 175±16 mg/dL blood and 95±10 mg/dL blood respectively. G6Pase mRNA levels and enzyme activites were decreased in liver of G6Pase siRNA-pDNA injected mice compared to pDNA injected control mice. Conclusion: G6Pase siRNA-pDNA treatment lead to lowering fasting blood glucose levels in diabetic mice. This represents that siRNA-pDNA injection sucessfully induced gene silencing in mice.