| Objective:To observe the efficacy of Danzhi Jiangtang capsule on clinical intervention in patients with T2DM-IR and its effects on insulin receptor substrate(IRS-1)and Sestrin2/m TOR/S6k1 signaling pathway in skeletal muscle tissue of GK rats and its underlying mechanism.Methods:1 Clinical study100 hospitalized patients with Type 2 Diabetes Mellitus with Insulin Resistance(T2DM-IR)who met the inclusion criteria in the medical records were screened.Classify hypoglycemic drugs as conventional oral hypoglycemic drugs into the western medicine group,while the patients which combined to use Danzhi Jiangtang Capsules(DJC,0.4g/capsule,4 capsules/time,3 times/day)on the basic treatment plan of the western medicine group were classified as Chinese medicine group.Using retrospective analysis methods,counted and analysis the general conditions of the two groups of patients before and after treatment,fasting blood glucose(FPG),2h postprandial blood glucose(2h PG),fasting insulin(FINS),homeostatic model insulin resistance index(HOMA-IR),quantitative Insulin sensitivity test index(QUICKI),glycosylated hemoglobin(Hb A1c),blood lipids(TG,TC,HDL-C,LDL-C),body mass index(BMI)and Chinese visceral fat index(CVAI),and observed the safety indicators of the two groups of patients.2 Animal experiment10 specific pathogen free(SPF)male Wistar rats were selected as the blank control group,weighing 190±10g,which given normal feed 50 SPF male spontaneous type 2diabetes(Goto-Kakizaki,GK)rats,weighing 180±30g,which given high-fat diet.Routine adaptive feeding of GK rats for 1 week,detected the random blood glucose and selected it above 16.7 mmol/L twice,combined with disease and syndrome modeling method to induce a T2DM-IR model of Qi-Yin deficiency and blood stasis.According to theranking number of blood glucose level,the GK rats were randomly divided into model groups,DJC high(DJC-H)dose group,medium(DJC-M)dose group,low dose group.(DJC-M)dose group and Western medicine group,10 rats in each group.The blank group and the model group were given normal saline(5ml/kg·d)during the experiment,the western medicine group was given metformin(0.1g/kg·d),and the high,medium and low doses of Chinese medicine were given DJC 0.99g/kg·d 、 0.49g/kg·d and0.25g/kg·d,intragastrically administered for 6 weeks in total.The blank control group was fed with basic feed until the end of the experiment,and the remaining five groups were fed with high-fat feed.During the experiment,observe the general condition of the rat,recording their body weight every 2 weeks,and measure fasting blood glucose(FBG)through tail vein blood sampling every week.Before and after the intervention,FINS was detected by blood sampling from the infraorbital vein,and calculated HOMA-IR and QUICKI.Six weeks after the intervention,the rats were taken,and the rats were fasted(anhydrous)for 12 hours 30 minutes after the last dose on the third day before taking the samples.Blood glucose was measured within 0 minutes through tail vein blood.Then,the rats were given 2.0 g/kg of 50% glucose solution by gavage.At 30 minutes,60 minutes,and 120 minutes after glucose administration,blood samples were collected from the tail tip of the rats,and blood glucose values at each time point were measured,calculated the area under the blood glucose curve(AUC)of each group.After anesthesia,the gastrocnemius muscle tissue was taken,and was using Western Blot method to detect the expression levels of Sestrin2,P-m TOR,m TOR,P-S6K1,S6K1,and IRS-1 in the gastrocnemius muscle tissue of rats.1 Clinical findings(1)100 cases were included in this research totaly,including 52 cases in the traditional Chinese medicine group and 48 cases in the western medicine group.The two groups had no obvious distinction in age,gender,course of diabetes,family history of T2 DM,waistline,BMI,and CVAI(P>0.05).(2)After treatment,the FPG,2h PG,Hb A1 c,FINS,and HOMA-IR of the two groups were all reduced(P<0.01);the traditional Chinese medicine group was evidently lower than the western medicine group’s FPG,Hb A1 c,FINS,HOMA-IR(P < 0.01);The QUICKI index of the traditional Chinese medicine group and the western medicine group both increased(P<0.05),and the degree of increase in the traditional Chinese medicine group was more obvious(P<0.01);(3)After treatment,the comparison of TC and TG in the two groups decreased(P<0.05),and the degree of decrease in the traditional Chinese medicine group was more obvious(P < 0.05),and the comparison between the two groups in HDL-C group increased(P < 0.05),and the degree of increase in the traditional Chinese medicine group was more obvious(P < 0.05);there was no statistically obvious distinction between the two groups after LDL-C treatment(P>0.05).(5)After treatment,the BMI and CVAI of the two groups were reduced(P<0.01 or P<0.05);the CVAI of the traditional Chinese medicine group was evidently lower than that of the western medicine group(P<0.05),and there was no obvious distinction in BMI(P<0.05).2 Animal Experiment Results(1)GK rats were in a state of continuous hyperglycemia,showing weight gain,slow response,decreased activity,constipation,rough fur,The above state was improved in different groups GK rats,especially in DJC-H group.(2)After modeling,GK rats in each group lost weight compared with the blank group(P<0.05),and the FBG level increased evidently(P<0.01).Compared with the model group,the body weight of the DJC-H group decreased after intervention(P<0.05);The FBG of rats in each treatment group was evidently reduced(P<0.01).Compared with the DJC group,the western medicine group had a higher reduction of FBG,but there was no obvious distinction compared with the DJC-L and DJC-H group(P>0.05).(3)Compared with the model group,the intervention of the DJC-H group,DJC-M group,and western medicine group can evidently improve the FINS level(P<0.01),but the distinction between the groups is not obvious(P>0.05);Intervention in the DJC-H group,DJC-M group or the western medicine group can evidently reduce the HOMA-IR level(P<0.05 or P<0.01),and the decrease in the western medicine group is more obvious(P<0.01);Intervention in the DJC-H group,DJC-M group,and western medicine group can all increase the level of QUICKI(P<0.01).The effects of the three groups on the level of plasma FINS and QUICKI in rats were improved more evidently by the western medicine group,but the distinction was not statistically obvious(P >0.05);The blood glucose level and AUC of rats in each treatment group decreased at each time point after meal(P>0.01),and the decrease in AUC in the western medicine group was more obvious(P>0.05).(4)Compared with the model group,the levels of TG,TC,HDL-C,LDL-C in each treatment group were improved,and the plasma levels of TG,TC,HDL-C,LDL-C in the DJC-H group and the western medicine group All were evidently improved(P<0.05 or P < 0.01),and the DJC-H group reduced LDL-C levels more evidently(P <0.01).(5)Compared with the model group,the relative expression of IRS-1 in the DJC-M,DJC-H and western medicine groups all increased evidently after intervention(P<0.05 or P < 0.01);the relative expression of Sestrin2 in each treatment group increased obviously(P<0.05 or P<0.01);the relative expression of P-m TOR in each treatment group decreased evidently(P<0.01 or P<0.05);the relative expression of m TOR and S6K1 in DJC-M group,DJC-H group and western medicine group The relative expression of P-S6K1 in the DJC-H group and the western medicine group was evidently reduced(P<0.05),and the relative expression of P-S6K1 in the DJC-H group and the western medicine group was evidently reduced(P<0.05).Conclusion:DJC can improve the blood glucose index of T2DM-IR patients with deficiency of both qi and yin with stasis,and further improve the body’s insulin sensitivity.It has a good therapeutic effect in adjust fat and maintain body weight.Its mechanism may be related to its intervention in Sestrin2/m TOR/S6K1 signaling pathway,which up-regulates Sestrin2,and reduces the expression of P-m TOR protein,further reduces the expression of P-S6K1 protein,enhances the expression of IRS-1 protein,and achieves the effect of ameliorating IR. |
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