Regulatory Effect of Qiwei Baizhusan on Liver Tissue Insulin PI3K/Akt Signal Pathway in Diabetic Mice / 中国实验方剂学杂志

Objective:To study the effect of Qiwei Baizhusan (QWBZS) on liver insulin phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） signal pathway of diabetic mice induced by high-fat diet and streptozotocin (STZ). Method:The methods of network pharmacology and animal experiments were used to study the hypoglycemic effect of QWBZS. Active chemical components of the drug and disease targets selected through public databases were used to construct the protein-protein interaction network (PPIN), and gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomics(KEGG) enrichment analysis was performed to identify relevant signal pathways in vivo. In the pharmacological experiment, the diabetic mice model was established through intraperitoneal injection with 80 mg·kg-1·d-1 STZ high-glucose, high-fat diet. The mice were divided into normal group (normal saline), model group (normal saline) and QWBZS group (18.7 g·kg-1·d-1). After 28 days, the hypoglycemic effect of the drug and its effect on serum total cholesterol (T-CHO), fasting insulin (FINS) and serum tumor necrosis factor-α (TNF-α) were determined. Western blot and Real-time fluorescence quantitative PCR (Real-time PCR) were used to detect protein and mRNA expressions of insulin receptor (IR), insulin receptor substrate-1 (IRS-1)，phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) in liver tissues． Result:A total of 36 active components in this drug were identified by network pharmacology. KEGG analysis suggested that QWBZS might play a role in reducing blood glucose by regulating PI3K Akt signal pathway. Compared with the model group, the levels of blood glucose, serum T-Cho and TNF-α of the intervention group were significantly lower (P<0.01), while the FINS of the intervention group was significantly higher (P<0.01). Protein and mRNA expressions of IR，IRS-1，PI3K and Akt in liver tissues of mice in QWBZS treatment group increased markedly (P<0.05，P<0.01). Conclusion:QWBZS could regulate the levels of blood glucose, TNF-α, T-CHO, and FINS in the serum of diabetic mice induced by high-fat diet and STZ. It can improve PI3K/Akt signal pathway of diabetic mice by regulating protein and mRNA expressions of IR，IRS-1，PI3K and Akt/PKB.

Comparison of insulin resistance scoring system with indirect methods of estimating insulin resistance in Indian type 2 diabetes subjects

Background: Identification of insulin resistance is very important in management of type 2 diabetes. The euglycemic insulin clamp method, intravenous glucose tolerance tests (IVGTT) and minimal model approximation of glucose (MMAMG) are standard methods of measurement of insulin resistance in research. However, they are impractical in clinical practice and are difficult to perform in population-based research studies. So, a simple scoring system was designed to estimate the insulin resistance. Methods: 200 type 2 diabetes individuals who attended Karnataka Institute of endocrinology and research outpatient department. Fasting plasma glucose, post prandial plasma glucose, fasting insulin, lipid profile, BMI, waist circumference and BP of these subjects were checked. Results: Out of 200 type 2 diabetes subjects 69.5% were males and age group ranging from 26 to 85 years. Duration of diabetes range from 0 to 20 years and 53% of patients had hypertension and 46.5% have hypertriglyceridemia. Insulin resistance calculated by KIER scoring system, HOMA-1, QUICKI, HOMA2 and Fasting Insulin was present in 82%, 63%, 63.5%, 33.5% and 37.5% 0f individuals respectively. KIER scoring system had a statistically significant correlation with HOMA and QUICKY indices. (P value < 0.001) Conclusions: (1) KIER scoring system detects insulin resistance in 82% of type 2 diabetes individuals. (2) HOMA 1 and QUICKI are identical and similarly HOMA 2 and fasting insulin levels are almost identical in estimation of insulin resistance. (3) The KIER scoring system designed is very simple and economical. It takes into consideration the different factors which contribute to insulin resistance.

Insulin resistance in obese and lean women with polycystic ovarian syndrome

Background: According to NIH criteria for PCOS, the estimated prevalence of this disorder has been reported to range from 4% to 10% of women in their reproductive years, which designates PCOS as the most common endocrinopathy of women. Insulin resistance is common in PCOS and obesity contributes an additional component to insulin resistance in obese PCOS.Methods: The study was a prospective study. One-hundred and twenty PCOS women were divided into two groups: Group O - obese (n = 60) and Group L - lean (body mass index [BMI] cutoff <23 kg/m2). Oral glucose tolerance test, serum fasting insulin and HOMA- IR were compared between these groups.Results: Impaired glucose tolerance was seen in 33.3 % of lean PCOS and 36.7% of obese PCOS women. 5% of lean PCOS and 10% of obese PCOS women had hyperinsulinemia. 38.3% of lean PCOS and 51.7% of obese PCOS women had insulin resistance. But the differences were not statistically significant. However, HOMA-IR and fasting insulin values showed a significant positive correlation with BMI.Conclusions: Both obese and lean women with PCOS are vulnerable to the problems of insulin resistance irrespective of BMI and insulin resistance shows a positive correlation with BMI.

Agreement of HOMA-IR,TyG index and FPG/FIns with GDR in patients with newly diagnosed T2DM / 中国糖尿病杂志

Objective To assess the agreement between homeostasis model assessment for insulin resistance index(HOMA-IR),a simple index of fasting serum triglyceride(TG)and plasma glucose(TyG index)and fasting plasma glucose(FPG)/fasting insulin(FIns)with glucose disposal rate(GDR)in patients with newly diagnosed type 2 diabetes(T2DM). Methods A total of 137 patients with newly diagnosed T2DM were enrolled.The levels of FPG,FIns,TG and GDR were measured in baseline. Agreement analysis was performed to assess their agreements. Results The bias and limit of agreement of HOMA-IR,FPG/FIns and TyG index with GDR were - 3.776(- 7.495 ~ - 0.055),- 8.428 (-25.311~ 8.456)and 1.075(- 2.598 ~ 4.749),respectively,and their intra-class correlation coefficients(ICC)were 0.797,0.503 and 0.236,respectively. Conclusion HOMA-IR,TyG index and FPG/FIns showed the acceptable agreement with the GDR. The poor reliability of FPG/FIns and TyG index(ICC＜0.6)limits its clinical application.

Insulin Resistance: Detection By Fasting Insulin In North Indian Obese Adults.

Background&objectives:Several studies have shown that obesity is closely related to Insulin resistance(IR). Insulin resistance has been suggested as a primary cause for metabolic syndrome. Identifying such individuals would help to prevent progression of comorbidities associated with IR. Hence present study was planned to assess the importance of Fasting Insulin(FI) as a measure of IR and to analyze its correlation with other indirect methods for the assessment of IR . Methods: Study was conducted in fifty obese and overweight subjects.Body Mass Index of all subjects was calculated . Blood glucose, and FI were assayed after twelve hours of fasting. Homeostasis model assessment (HOMA) and Quantitative insulin sensitivity check indices (QUICKI) were calculated. Results: Present study showed that 90% of subjects had IR by HOMA and QUICKI.Correlation of FI with HOMA and QUICKI was statistically significant (P < 0.05). FI test had significant sensitivity and specificity when compared with HOMA and QUICKI indices. Validity of FI was further analyzed by Cohen’s kappa test and had good agreement (κ =0.67). Conclusion: FI was sensitive and also specific as HOMA and QUICKI in assessment of IR in obese. Thus, FI can be used as a simple test and feasable tool to detect IR in obese subjects. [AnshuKhatri NJIRM 2016; 7(5):1-4]

Fasting insulin resistance indices and metabolic syndrome in diabetes and HIV infected subjects.

Diabetes Mellitus and HIV remain two major clinical conditions of public health importance especially in developing countries.HIV impairs normal immune response against malignant infections and destroy many organs impairing their functions including the pancrease. Ordinarily, the pancrease performs exocrine functions thus producing insulin from the beta cells of the islets of langerhan aiding in nutrient metabolism.The beta cells of islet can be destroyed by the T-lymphocytes resulting to clinical diabetes characterized by hyperglycemia Diabetes and HIV have been associated with metabolic dearrangement particularly lipodystrophy.It was in this line that we designed a study to monitor fasting insulin resistance indices and metabolic syndrome in120 subjects of age 30-55 years comprises of 50 HIV –Infected,50 Type 2 Diabetes and twenty apparently healthy subjects who served as control attending Nnamdi Azikiwe University Teaching Hospital Nnewi(NAUTH).The blood samples collected from the subjects were used for evalution of lipid profile Tryceride(TG) ,low density lipoprotein-cholesterol(LDL-C) and high density lipoprotein – cholesterol (HDL-C), Fasting blood sugar was measured using routine standard method while fasting insulin was done using indirect ELISA method .The insulin resistance indices were also evaluated. Data were analyzed for the statistical significance using one way ANOVA. The fasting insulin, fasting blood sugar, triglyceride and LDL-C were remarkably higher inType 2 Diabetic subjects compared to control P <0.01. Equally observed in the study was that the fasting insulin, fasting blood sugar and triglyceride were higher in HIV subjects compared to control subjects P <0.01.Though, the HDL-C was quite reduced in HIV –Infected subjects P <0.01. The finding of this study has revealed further lipid and carbohydrate distortion in both diabetic and HIV subjects which might place individuals to high risk of atherosclerosis due to reduced HDL-C if not checked.

Association of serum apolipoprotein A5 with leptin and insulin in obese children / 中华内分泌代谢杂志

Totally 79 obese children and 64 children with normal body weight were included in the present study.Serum apolipoprotein A5 (ApoA5) and leptin levels were determined by ELISA and fasting insulin by RIA.The clinical data including height,body weight,waist circumference,blood pressure,blood lipid,blood glucose,etc,were collected.Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.The results showed that compared with normal weight children,both serum leptin and insulin levels were significantly raised in obese children [19.15 (13.01 ～ 25.08) ng/ml vs 3.29 (1.45 ～ 6.02) ng/ml and 15.44 (12.05 ～ 20.26) μg/L vs 10.12 (8.60 ～ 12.60) μg/L,both P＜0.01],while ApoA5 level was significantly lowered [134.5 (105.9 ～ 172.7) ng/ml vs 2005.9(164.3 ～ 265.3) ng/ml,P＜0.01].Serum ApoA5 was negatively correlated with serum leptin and insulin (both P＜0.01).

The association between insulin resistance and prostatic hyperplasia / 中华老年医学杂志

Objective To evaluate the relationship between insulin resistance and benign prostatic hyperplasia (BPH).Methods Totally 150 male patient from the Department of Geriatrics in Peking University Hospital were included in this study.Blood pressure,body weight,body height,body mass index (BMI) were measured and calculated.Biochemical analyses including serum fasting levels of insulin(FINS),glucose,total cholesterol,triglycerides,low-density lipoprotein cholesterol,high density lipoprotein cholesterol,and prostate-specific antigen (PSA) were performed.Total prostate volume (PV) were measured by ultrasound.Results PV and annual prostate growth rate were more increased in insulin resistance group(40 cases) compared with insulin sensitivity group(110 cases) (t=2.91,3.71 respectively,both P＜0.01).Along with the levels of FINS,HOMA-IR and PSA were increased,the prostate volume was enhanced (t=-3.02,-2.88,-2.84 respectively;all P ＜0.05).PV was positively correlated with insulin resistance,serum fasting insulin and PSA (r=0.16,0.16,0.35;all P＜0.05),while annual prostate growth rate was positively related with insulin resistance,serum fasting insulin,PSA and BMI (r =0.22,0.21,0.24,0.19 ; all P ＜ 0.05).Conclusions Insulin resistance and fasting insulin plays roles in the pathogenesis of prostatic hyperplasia.

The association of fasting insuline and insuline resistance with benign prostatic hyperplasia / 中国综合临床

Objective To reveal the effect of fasting insuline(FINS) and insuline resistance(IR) in the process of benign prostatic hyperplasia(BPH). Methods One hundred and seventeen outpatients( ≥60 ys)with BPH from geriatric department were enrolled into the study. The patients were divided into groups according to their FINS and insulin resistance index (HOMA-IR). The indices of BPH, including volume of prostate ( PV ),prostate specific antigen( PSA ), international prostate symptom score (IPSS), course of BPH were analyzed in both groups. Results The PV ( [ 56. 46 ± 26. 88 ] ml vs [ 44. 84 ± 17.66 ] ml, P = 0. 017 ) and the course ( [ 18. 00 ± 6. 91 ] years vs [ 13.93 ± 7. 74 ] years, P = 0. 031 ) were significantly greater in BPH combined hyperinsulinemias(HINS) group than the BPH with normal FINS group;but we found no significant differences in the comparisons of serum PSA level or IPSS between two groups. The PV( [54. 17 ± 25.38 ] ml vs [42. 26 ±14. 15]ml,P =0. 004)and the course([ 16.58 ±7. 65] years vs [13.49 ±7. 59] years,P = 0. 036) were also significantly greater in BPH combined insuline resistance gruop than the insulin sensitivity group, again we found no significant differences in the comparisons of serum PSA level or IPSS between two groups. Conclusion FINS and IR are risk factors of progressed BPH and can promote the progress of BPH.

The Expression of Resistin in Adipose Tissues of Patients with Polycystic Ovary Syndrome and Insulin Resistance / 华中科技大学学报（医学）（英德文版）

The relationship between the expression of resistin in polycystic ovary syndrome (PCOS) and insulin resistance was investigated. The plasma resistin concentrations in 35 patients with PCOS and 40 controls were measured by ELISA. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and fasting insulin (FIN) were tested by radioimmunoassay. Insulin resistance index (HOMA-IR) was calculated. Fasting plasma glucose (FPG) was determined by oxidase test. Western blot and reverse transcriptase PCR (RT-PCR) methods were used to detect the expression of resistin in adipose tissues.The levels of plasma resistin, LH, LH/FSH and FIN and HOMA-IR in patients with PCOS were sig-nificantly higher than those in control group (all P<0.05). Plasma resistin was correlated positively with FPG, FIN, HOMA-IR, LH and LH/FSH (r=0.56, 0.60, 0.65, 0.48, and 0.42 respectively). Resistin pro-tein and mRNA expression levels in patients with PCOS were significantly higher than those in normal tissues (all P<0.01). It was concluded that resistin might be involved in the pathogenesis of insulin re-sistance of PCOS.

Levels of serum retinol-binding protein 4 and related factors in type 2 diabetic patients / 中国医师进修杂志

Objective To investigate the levels of serum retinol-binding protein 4 (RBP4 )and related factors in type 2 diabetic patients. Methods Eighty type 2 diabetic and patients 30 non-diabetic subjects were recruited into obese-diabetic group [body mass index (BMI) 1525 kg/m~2],normal-weighted diabetic group(BMI < 25 kg/m~2)and control group(BMI < 25 kg/m~2). Serum adiponectin(APN), RBP4 and hemoglobin A_1c (HbA_1c)triacylglycerol (TG),total cholesterol (TC).high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C)and were measured on fasting samples. BMI, waist/hips girth ratio (WHR) and insulin resistance index (HOMA-IR) were calculated. The correlation between RBP4 and other factors was analyzed. Results The concentration of RBP4 was significantly increased in obese-diabetic group and normal-weighted diabetic group compared with that in control group [ (30.02 ± 5.32), (20.10 ± 5.45), (12.02 ± 3.45) mg/L] (P < 0.01). The concentration of RBP4 was higher in obese-diabetic group than that in normalweighted diabetic group (P < 0.01). Univariate analysis showed serum RBP4 was positively associated with TG,BMI,FBG, WHR,FINS,HOMA-IR and negatively associated with APN (r = 0.225, 0.697, 0.323,0.557, 0.272, 0.461, -0.398). Conclusions The concentration of RBP4 is significantly higher in type 2 diabetic patients compared with that in normal subjects. RBP4 possibly plays an important role in the insulin resistance and the occurrence and development of type 2 diabetes.

The Association of Abdominal Fat with Serum Insulin and Atherogenic Index for Obese Females

BACKGROUND: The purpose of this study was to find an independent relationship between waist circumference/waist-to-hip ratio which estimates abdominal fat and fasting insulin/atherogenic index which is a predictor of coronary heart disease in obese women. METHODS: The subjects were 80 obese (BMI > or = 25 kg/m2) women. Whole body fat was estimated by body fat mass, % body fat using bioelectrical impedence, and by BMI. Abdominal fat was measured by waist circumference (WC) and waist-to-hip ratio. Fasting insulin was examined and atherogenic index was defined asthe ratio of serum total cholesterol to HDL-cholesterol. Independent association between abdominal fat and insulin/AI was analyzed using partial correlation, multiple regression and Hotelling t-test. RESULTS: Among subjects, 85.7% of obese women had WC greater or equal to 80 cm. The mean BMI was 30.3 kg/m2. The partial correlations between whole body fat and insulin/AI were not significantly different from the partial correlations between abdominal fat and insulin/AI. When age and height were adjusted, partial correlations between abdominal fat and insulin were 0.38 and 0.39. The partial correlations were reduced to 0.15-0.29 after further adjusting for whole body fat. Age and height-adjusted partial correlations between abdominal fat and AI were 0.34 and 0.36. The partial correlations were reduced to 0.11-0.17 when whole body fat was additionally adjusted. Whole body fat explained 9.9-13.7% for variability of insulin; abdominal fat explained 14.2% and 15.9%. Whole body fat explained 12.5-12.8% for variability of AI and abdominal fat explained 11.9%. CONCLUSION: Most of the obese women showed abdominal obesity. Abdominal fat did not seem to be independently associated with fasting insulin and atherogenic index.