ABSTRACT
The present study investigated the therapeutic efficacy and potential mechanism of Jinqi Jiangtang Tablets(JQJT) on pancreatic β cell dysfunction based on network pharmacology and molecular docking technology. TCMSP platform was used to retrieve the chemical components and targets of the three Chinese herbal medicines of JQJT. The genes were converted to gene symbol by the UniProt, and its intersection with targets related to pancreatic β cell function in GeneCards and CTD databases was obtained. The drugs, active components and common targets were imported into Cytoscape 3.8.2 to plot the drug-component-target network. The main effective components and targets were obtained by software analysis. The drug targets and targets related to pancreatic β cell function were imported separately into the STRING platform for the construction of protein-protein interaction(PPI) networks. The two PPI networks were merged by Cytoscape 3.8.2 and the key targets were obtained by plug-in CytoNCA. The targets obtained from drug-component-target network and PPI networks were imported into DAVID for GO analysis and KEGG enrichment analysis. AutoDock was used to carry out molecular docking of main active components and core targets and Pymol was used to plot the molecular docking diagram. The results showed that there were 371 active components and 203 targets related to JQJT and 2 523 targets related to pancreatic β cell damage, covering 136 common targets. The results revealed core targets(such as PTGS2, PTGS1, NOS2, ESR1 and RXRA) and effective key components(such as quercetin, kaempferol, luteolin, β-carotene and β-sitosterol). KEGG enrichment analysis indicated that apoptosis, inflammation, and other signaling pathways were mainly involved. Molecular docking results showed that the main active components could spontaneously bind to the targets. This study preliminarily revealed the mechanism of JQJT in improving pancreatic β cell damage through multi-component, multi-target and multi-pathway, and provided a theoretical basis for JQJT in the treatment of pancreatic β cell dysfunction.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Insulin-Secreting Cells , Medicine, Chinese Traditional , Molecular Docking Simulation , Tablets , TechnologyABSTRACT
Objective: To investigate the characteristics of insulin secretion function and sensitivity and blood glucose disposition capacity in the prediabetes populations. Methods: A total of 1 317 subjects were enrolled in this study, including 382 with normal glucose tolerance (NGT) and 935 with pre-diabetes. All pre-diabetes populations were divided into seven subgroups according to the cut-off points of 2010 American Diabetes Association standards. Homeostasis model assessment (HOMA) was used to access baseline insulin secretion (HOMA-β) and insulin sensitivity (HOMA-IR). Insulin secretion and sensitivity after glucose load were evaluated by area under curve (AUC) for insulin/AUC for glucose (AUCINS120/AUCGLU120) and insulin sensitivity index (ISI) calculated from Cederholm formula, respectively. Disposition index (DI) was used to reflect blood glucose disposition capacity. Results: The most common type of pre-diabetes was impaired fasting glucose (IFG) combined with impaired glucose tolerance (IGT) and glycated hemoglobin A1c (HbA1c ) 5.7%-6.4%, followed by isolated IGT, while the proportion of isolated IFG was the lowest. The insulin sensitivity of isolated HbA1c 5.7%-6.4% group was better than that of isolated IFG group, isolated IGT group, and IFG combined with IGT group (P<0.05). And its β-cell function was similar with the other subgroups. The DI value of isolated HbA1c 5.7%-6.4% group was about 1.5 times of that of isolated IGT group and IFG combined with IGT group (P=0.000), which was similar with isolated IFG group. The function of β cell or insulin sensitivity in the pre-diabetes subjects with HbA1c 5.7%-6.4% was further damaged compared with the pre-diabetes people whose HbA1c were lower than 5.7%. Conclusion: Different types of pre-diabetes are significantly heterogeneous under new diagnostic criteria, and further prospective studies with a larger sample size are needed to clarify whether HbA1c 5.7%-6.4% is suitable as a diagnostic criteria for pre-diabetes in Chinese population.
ABSTRACT
To investigate the effects of metformin on pancreatic β-cell function and its possible mechanism, high fat diet-induced type 2 diabetic C57BL/6J mice were divided into two groups according to fasting blood glucose (FBG), glucose decreasing rate at 40 min of insulin tolerance test, triglycerides (TG), cholesterol (CHO) and body weight (BW). The C57 mice were gavaged with water or metformin for 58 days. β-Cell function was evaluated by oral glucose tolerance test and hyperglycemic clamp. Genes and proteins related to pancreas proliferation, lipid metabolism and endoplasmic reticulum stress were investigated. Compared with the model group, metformin group exhibited a reduction in the body weight (PPPPPPdx-1, Pβ (Lxr-β, PPPP<0.05) were also down-regulated. These results suggest that metformin could improve the insulin secretion function of type 2 diabetic C57BL/6J mice. The mechanism of the action may rely on its improvement of pancreas cell proliferation, lipid metabolism and amelioration of endoplasmic reticulum stress.
ABSTRACT
Objective To investigate the relationship of pancreatic β-cell function and insulin resistance with microalbuminuria in a cross -sectional study of patients with type 2 diabetes.Methods A total of 524 partici-pants with type 2 diabetes were recruited in this cross -sectional study.All subjects'height,weight,waist circumfer-ence and blood pressure were measured.Venous blood samples were drawn to measure fasting plasma glucose (FPG), fasting lipids,glycated hemoglobin A1c (HbA1c),fasting C -peptide (FPC).24h -urine was collected to measure urinary albumin excretion rate (UAER).Homeostasis model assessment of pancreatic β-cell function (HOMA -B) and insulin resistance (HOMA -IR)were estimated using fasting plasma C -peptide.According to HOMA -B quar-tile,the subjects were divided into four groups,including q1 -q4.According to HOMA -IR,the subjects were also divided into four groups,including Q1 -Q4.We assessed the crude associations across quartiles of these data with demographic and clinical parameters using a nonparametric test for trend across ordered groups (trend using Stata software).Multivariable logistic regression analysis was performed to assess the relationships of pancreatic β-cell function and insulin resistance with microalbuminuria in patients with type 2 diabetes.Results Trend test showed that UAER gradually reduced with increase of HOMA -B.The UAER values in subjects with q1,q2,q3 and q4 were 8.92(5.53 -28.65),8.55(5.52 -20.95),7.57(4.79 -19.83)and 7.84(5.23 -14.38)μg/min,respectively, and the trend was statistically significant(z =-2.1,P <0.05 ).With HOMA -IR increasing,UAER gradually increased.The UAER values in subjects with Q1,Q2,Q3 and Q4 were 6.73(4.85 -16.52),8.61 (5.2 -20.37), 8.31(4.88 -27.04),8.75(6.03 -25.21)μg/min,respectively,and the trend was also statistically significant(z =2.41,P <0.05).Multivariable logistic regression analysis showed that subjects with the highest quartile of HOMA -B had lower possibility of microalbuminuria than patients with the lowest quartile of HOMA -B (adjusted OR q4 vs. q1 =0.39,95% CI:0.20 -0.76,Wald =7.59,P =0.006).Subjects with the highest quartile of HOMA -IR had higher risk of microalbuminuria than those with the lowest quartile of HOMA -IR (adjusted OR Q4 vs.Q1 =2.00, 95% CI:1.08 -3.72,Wald =4.84,P =0.028).Conclusion Insulin resistance is associated with an increased prevalence of microalbuminuria in type 2 diabetes,while improved pancreatic β-cell function is linked to decreased rates of microalbuminuria for those patients.
ABSTRACT
[Summary] The effects of lipid components on insulin secretion in patients with type 2 diabetes(T2DM) and control subjects were explored. The results demonstrated that in control group, disposal index( DI)0 was positively correlated with high density cholesterol(HDL-C), while DI30 was negatively correlated with total cholesterol(TC), triglycerides( TG) and low density cholesterol ( LDL-C), and DI120 was also negatively correlated with TC and LDL-C. In T2DM group, DI0 was negatively correlated with TC and LDL-C, DI30 was negatively correlated with TC, TG, LDL-C and TG/ HDL-C, DI120 was negatively correlated with TC, TG, LDL-C and TG/ HDL-C.
ABSTRACT
Objective To understand effects of hyperthyroidism on glucose metabolism and its clinical significance.Methods 65 patients admitted in Xixi Street Community Health Center were divided into 3 groups according to their accompanying disease:group A,22 cases of hyperthyroidism accompanying with diabetes mellitus,group B,23 cases of diabetes,and group C,20 cases of hyperthyroidism.Group A and B were treated with intensive insulin therapy.Group B patients took oral methimazole or propylthiouracil.Group C patients were treated with conventional treatment of hyperthyroidism.All patients were treated for three weeks.Fasting plasma glucose (FPG) and postprandial 2h plasma glucose (2hBG),heart rate,serum triiodothyronine three (TT3),serum total thyroxine (TT4)and other indicators were recorded before and after treatment.Results After intensive insulin therapy,FPG and 2h BG of patients in group A and B were controlled in ideal range.After treatment,TT3 and TT4 decreased significantly faster than before treatment(P ＜ 0.05).Patients in group A needed more insulin than in group B to bring the blood glucose to the normal level(P ＜0.05),but after three weeks,patients in group A and group B needed similar dose of insulin.Patients in group A needed more time than patients in group B to bring down the blood glucose level.(P ＜ 0.05).In addition,change of heart rate in group A before and after treatment were greater than the other two groups,and patients' heart rate in group A returned to normal after three weeks of treatment.(P ＜ 0.05).Conclusions Thyroid hormones affects glucose metabolism.Diabetes complicated with hyperthyroidism mainly caused by patient's abnormal glucose metabolism and insulin resistance.Intensive insulin therapy for these patients can improve β cell function,lower blood glucose rapidly.Compared with diabetes patient without complication of hyperthyroidism,early intensive insulin therapy should be considered.
ABSTRACT
Objective To observe and compare the variation of insulin resistance and pancreatic β-cell function in pregnant women with abnormal and normal glucose metabolism during the first,second,and third trimesters,and to explore the feasibility of early diagnosis of gestational diabetes mellitus(GDM).Methods This is a prospective study.507 pregnant women with regular antenatal care from February 2009 to March 2010 were included in the study.Based on the results of oral glucose tolerance test,the patients with GDM consisted of 58,86,and 66 subjects respectively in the first,second,and third trimesters.The control group included 72,164,and 66 subjects respectively in the first,second,and third trimesters.Homeostasis model assessment insulin resistance index( HOMA-IR),homeostasis model assessment β-cell function (HOMA-β),area under curve of glucose (AUCG),area under curve of insulin ( AUCI ),30-minute insulin increase to 30-minute glucose increase ( △I30/△G30 ),and insulin sensitivity index composite(ISIcomp) were calculated for the evaluation of insulin resistance and pancreatic β-cell function.Results ( 1 ) AUCG and AUCI in the GDM group were statistically higher than those in control group while △I30/△G30and ISlcomp in the GDM group were statistically lower than those in the control group during the first trimester(P＜0.05),but HOMA-IR showed no statistically significant difference between two groups.In the GDM groups HOMA-IR,AUCG,and AUCI were statistically higher,whereas △I30/△G30 and ISIcomp were statistically lower than those in the control groups during the second and third trimesters (P ＜ 0.05 ). HOMA-β showed no statistically significant differences between the GDM groups and control groups during 3 trimesters.( 2 ) During thefirst,second,and third trimesters,blood glucose reached its peak by 0.5 h in the oral glucose tolerance test,and insulin reached its peak by 0.5-1 h in the control groups; while in the GDM groups the respective figures were 1 h and 2 h.Conclusions The insulin resistance in GDM patients diagnosed during the first,second,and third trimesters was higher than in pregnant women with normal glucose metabolism,and the peaks of blood glucose and insulin reached in oral glucose tolerance test were respectively delayed.The impaired pancreatic β-cell insulin secretion in GDM patients was present from early pregnancy.Thus for high-risk groups,oral glucose tolerance test during early pregnancy will be helpful for screening abnormal glucose metabolism.
ABSTRACT
Based on the results of oral glucose tolerance test( OGTT )and the levels of 1-h plasma glucose ( 1 hPG),793 subjects were classified into three groups:583 with NGTN ( normal 1 hPG in OGTT),127 with NGT1 H( higher 1 hPG in OGTT) and 83 with IGT( impaired glucose tolerance).NGT1H group had large waist circumference,higher body mass index,fasting plasma glucose( FPG),triglyceride,and lower high density lipoprotein-cholesterol than those of NGTN group.NGT1 H group had higher homeostasis model assessment insulin index ( 1.2 ± 0.6),lower homeostasis model assessment β3 ( HOMA-β ) (4.5 ± 0.7 ) and insulinogenic index (2.1 ±0.7) than those of NGTN group(0.5 ±0.6,4.8 ±0.7,2.7 ±0.9,respectively,all P ＜0.05 ).HOMA-β of NGT1 H group was higher than that of IGT group(4.5 ±0.7 vs.4.4 ±0.6,P ＜0.05 ).The results indicate that 1 hPG in OGTT may identify a condition of glucose metabolic abnormalities characterized by insulin resistance and reduced β-cell function.
ABSTRACT
Objective To investigate relationship between insulin sensitivity and beta-cell function with body mass index (BMI) and age in patients with newly diagnosed type 2 diabetes mellitus (T2DM).Methods Totally, 304 patients with T2DM newly-diagnosed at admission to the first hospital affiliated to Nanjing Medical University, Jiangsu province, during 2006 to 2007 were recruited in the study. The patients were divided into three groups based on WHO criteria of obesity in Asia Pacific Region in 2003, 68 cases with normal weight ( 18. 5≤ BMI ＜ 23.0), 69 in overweight (23.0 ≤ BMI ＜ 25.0), and 167 in obesity (BMI≥25.0). Fasting serum glucose, glycesylated hemoglobin Alc (HbAlc) and lipids were measured for all the subjects, as well as oral glucose tolerance test (OGTr), C-peptide releasing tests and determination of serum insulin performed. Homeostasis model assessment of insulin resistance index (HOMA-IR), insulinogenic index (AI30/AG30) and modified beta-cell function index (MBCI) werecalculated to evaluate their insulin sensitivity and beta-cell function of the islets. All these parameters werecompared between the three groups and subgroups. Results HOMA-IR and MBCI were significantly higherin T2DM patients with obesity than those in the groups with normal weight and over-weight ( P < 0. 05 ).AI30/AG30 in obesity group was significantly higher than that in the group with normal weight (P <0. 05).Multiple linear regression analysis showed that BMI independently correlated with HOMA-IR ( P < O. 05 ).Sub-group analysis showed that △I30/△G30 and MBCI were significantly higher in those aged 60 years and over with obesity than those in the groups aged less than 60 years ( P ＜ 0. 05 ). Conclusions Non-obese patients with newly diagnosed T2DM have more severe impaired insulin secretion than that in obese ones,and their insulin resistance increases with BMI. Age has no significant correlation with pancreatic beta-cell function or insulin sensitivity.
ABSTRACT
Eleven-week-old SD rats were randomized into control and calorie restriction group. The pancreatic β cell function and oxidative stress indexes in the two groups were compared after 24-week intervention. The results showed that calorie restriction, which started from young age, improved the early insulin secretion after glucose loading and alleviated the oxidative stress in adult rats, which wag related to the reduction of body weight.
ABSTRACT
Objective To investigate the relationship between the serum ghrelin level and β-cell function after treatment of patients with newly diagnosed type 2 diabetes mellitus.Methods 34 patients with newly diagnosed type 2 diabetes mellitus were divided into three groups of pre-treatment(DM0),two weeks after treatment(DM1)and six months after treatment(DM2).Intravenous glucose tolerance tests(IVGTT)were performed and blood glucose,HbA1C,ghrelin,insulin were measured during the study.Insulin sensitivity was assessed by homeostasis model assessment(HOMA).Results(1)Compared with DM0 group,beta-cell function and the mean AUC of insulin were dramatically improved in groups of DM1 and DM2(all P<0.05).(2)Compared with DM1 and DM2,ghrelin levels and the mean AUC of ghrelin in DM0 groups were lower(all P<0.05).(3)Only positive correlation between ghrelin and HOMA-β(r=0.446,P<0.05),and negative correlations of ghrelin with glucose(r=-0.274,P<0.05),insulin(r=-0.35,P<0.05)and BMI(r=-0.276,P<0.05)were found after six months of treatment.Conclusions Ghrelin might play an important role in the pathogenesis and progress of type 2 diabetes mellitus.