ABSTRACT
Objective:To investigate the association of serum protein kinase Cε(PKCε)activity with insulin resistance in elderly patients with concurrent type 2 diabetes mellitus(T2DM)and non-alcoholic fatty liver disease(NAFLD).Methods:Clinical data of 229 patients with T2DM admitted to the Department of Geriatric Endocrinology of the Second Affiliated Hospital of Xi'an Jiaotong University from October 2017 to October 2018 were retrospectively analyzed.Patients were divided into the T2DM group(T2DM patients without NAFLD, n=112)and the T2DM+ NAFLD group(T2DM patients with NAFLD, n=117). Healthy elderly subjects who underwent physical examination during the same period served as the control group(n=110). Clinical data and laboratory results were compared between the three groups.Serum PKCεactivity was measured by enzyme-linked immunosorbent assay, and the correlation between serum PKCεactivity and insulin resistance was analyzed statistically.Results:Serum PKCεactivity and HOMA-IR were higher in the T2DM+ NAFLD group than in the T2DM group and the control group[PKCε: (195.5±62.1) μg/L vs.(188.7±61.2 )μg/L and (89.1±20.2 )μg/L, F=9.76, P=0.010; HOMA-IR: 12.5±7.9 vs. 14.1±5.7 and 5.8±4.1, F=10.21, P=0.010]. Pearson correlation analysis revealed that serum PKCεactivity, HOMA-IR and TG were positively correlated with T2DM+ NAFLD( r=0.339, P=0.01; r=0.305, P=0.01; r=0.329, P=0.01)and that serum PKCεactivity was positively correlated with HOMA-IR and triglyceride( r=0.339, 0.305 and 0.329, P=0.01). Logistic regression analysis showed that serum PKCε activity, HOMA-IR and triglycerides were risk factors in the T2DM+ NAFLD group, and the regression coefficients were 0.849, 0.022 and 0.710, respectively.Increased serum PKCεactivity was an independent influencing factor for T2DM+ NAFLD. Conclusions:Elevated serum PKCεactivity is positively correlated with insulin resistance in elderly T2DM patients with NAFLD.Reducing serum PKCεactivity and improving insulin sensitivity will help to delay or reverse the development of T2DM and NAFLD.
ABSTRACT
Objective To investigate the treatment effect of ginsenoside compound K (CK) on glucose and lipid metabolism in diabetic mellitus mice and the potential molecular mechanism.Methods A total of 36 mice were randomly divided into normal group,diabetic mellitus group,CK treatment groups (100 or 200 mg/kg body weight),dimethyldiguanide group and p38MAPK pathway agonist P79350 group,with 6 mice in each group.Diabetic mice were established by intraperitoneal injection of streptozotocin combined with high-fat diet,and CK with different doses was administrated by gastric lavage for consecutive 8 weeks.The levels of fasting blood-glucose,triglyceride (TG),total cholesterol (TC),high-density lipoprotein (HDL C),fasting serum insulin were measured,and the insulin sensitive index (ISI) was calculated in different treatment groups.Glucose tolerance was detected by oral glucose tolerance test.The protein levels of ASK1,p-ASK1 and p38,p-p38,was detected by Western blot.The mRNA expression of apoptosis signal regulating kinase-1 (ASK1) was detected by real-time quantitative PCR.Results The fasting blood-glucose,TG,TC,HDL C,fasting serum insulin and ISI were (28.31 ± 3.40),(1.90 ± 0.28),(5.00 ± 0.72),(0.50 ± 0.08),(9.01 ± 1.70) mmol/L and-6.42 ± 0.76 in diabetic mice,respectively.The corresponding values were (12.02± 1.81),(0.97 ±0.09),(2.90 ±0.49),(0.91 ±0.08),(15.12 ± 1.93)mmol/L and-4.33 ± 0.46 in 200 mg/kg CK treatment diabetic mice,and were (12.87 ± 2.61),(1.09 ± 0.11),(3.08 ± 0.27),(0.87 ±0.08),(14.97 ± 1.27) mmol/L and-4.42 ± 0.35 in dimethyldiguanide group.All of the fasting blood-glucose,TG and TC in CK treatment groups were significantly lower than those of diabetic mellitus group (P ＜0.05 or ＜0.01),but the fasting serum insulin and ISI in CK treatment groups were significantly higher than that of diabetic mellitus group (P ＜ 0.05 or ＜ 0.01).There were no significant difference between 200 mg/kg CK treatment group and dimethyldiguanide group.The mRNA levels of ASK1 in normal group,diabetic mellitus group and 200 mg/kg CK treatment group were 1.00 ± 0.07,2.52 ± 0.14 and 1.25 ± 0.08,respectively.The mRNA levels of ASK1 in diabetic mellitus group and 200 mg/kg CK treatment group were significantly up-regulated than that of normal group (P＜0.01),but there was no significant difference between 200 mg/kg CK treatment group and diabetic mellitus group in the mRNA levels of ASK1.There was no significant difference in the protein expression levels of ASK1 and p38 among normal group,diabetic mellitus group and 200 mg/kg CK treatment group,but the protein expression levels of p-ASK1 and p-p38 were significant higher in diabetic mellitus group than that in normal group (P＜0.05 or ＜0.01),and were significant lower in 200 mg/kg CK treatment group than that in diabetic mellitus group (P ＜ 0.05 or ＜ 0.01),and were no significant difference between 200 mg/kg CK treatment group and normal group.Conclusions Ginsenoside CK effectively attenuates diabetic mellitus in mouse model,possibly by inhibiting the phosphorylation of ASK1-p38MAPK signaling pathway.