Jiangzhi Capsule Improves Fructose-induced Insulin Resistance In Rats: Association With Repair Of The Impaired Sarcolemmal Glucose Transporter-4 Recycling

Objective To observe the effect of Jiangzhi Capsule(JZC)on improving fructose-induced insulin resistance and to explore the possible mechanism.Background Jiangzhi Capsule,originated from an experienced formula in traditional Chinese Medicine,has been listed and used for the management of metabolic abnormalities in Australia for a long time.To better understand Jiangzhi Capsule,this study investigated its effect on insulin resistance.Materials and methods Thirty-three rats were divided initially into 2 groups: normal control(n=6)and fructose group(n=27).Water control was free access to water,and fructose group was free access to 10% fructose solution(w/v,preparation every day)for 7 weeks.This fructose group had continued free access to 10% fructose solution for the duration of the study but was further divided into the following 3 groups(n=9each)7 weeks after study commencement: model group(10% fructose solution),and low-and high-dose JZC(25mg/kg and 100mg/kg)groups.At the end of week 13,oral glucose tolerance test(OGTT)was performed.Animals were weighed and euthanized after being fasted over-night at the end of week 14.Enzymatical method was used for the examination of plasma glucose,triglyceride(TG),total cholesterol(TC).Determination of plasma insulin content by ELISA.The protein expression was detected by Western blot and/or immunohistochemistry.Gene expression was analyzed by Real-time PCR.Results Treatment with Jiangzhi Capsule(100 mg/kg)attenuated fructose overconsumption-induced increases in basal plasma insulin concentrations,the homeostasis model assessment of insulin resistance index(HOMA-IR)and the adipose tissue insulin resistance index(Adipo-IR)in rats.The increased plasma glucose concentrations during oral glucose tolerance test were also inhibited.Furthermore,Jiangzhi Capsule had a trend to attenuate the decreased ratios of glucose and non-esterified fatty acids to plasma insulin concentrations.Mechanistically,this insulin-sensitizing action was accompanied by normalization of the downregulated sarcolemmal glucose transporter(GLUT)-4 protein expression and the decreased phosphorylated Akt to total Akt protein ratio in gastrocnemius.Conclusions These results suggest that Jiangzhi Capsule ameliorates fructose-induced insulin resistance with a link to repair of the impaired sarcolemmal GLUT-4 recycling through modulation of the ratio of phosphorylated Akt to total Akt in gastrocnemius.Our findings provide an evidence-based and mechanistic understanding of Jiangzhi Capsule for the management of insulin resistance-associated disorders.