Mechanism of Huanglian Wendan Decoction in improving impaired glucose tolerance based on skeletal muscle NLRP3/caspase-1/IL-1β, IL-18 pathway / 中国中药杂志

This study investigated the mechanism of improving impaired glucose tolerance(IGT) of rats by Huanglian Wendan Decoction from the perspective of the skeletal muscle Nod-like receptor protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/interleukin-1β(IL-1β), interleukin-18(IL-18) pathway. Healthy male SD rats were fed with the diet containing 45% fat for 20 weeks, accompanied by a high-temperature and high-humidity environment and an inactive lifestyle, for the establishment of the IGT rat model. The rats were divided into the blank control group, model control group, metformin hydrochloride group(positive drug group, 0.05 g·kg~(-1)·d~(-1)) and Huanglian Wendan Decoction group(7.8 g·kg~(-1)·d~(-1)). After continuous intragastric administration for 4 weeks, the obesity and glycemic indexes of all the rats were measured. The fasting serum insulin(FINS) level was determined by ELISA, with the insulin sensitivity index(ISI) and insulin resistance index(IRI) calculated. The mRNA and protein expression le-vels of nuclear factor kappaB(NF-κB), NLRP3, caspase-1, IL-1β and IL-18 in skeletal muscle tissue were detected by real-time polymerase chain reaction(PCR), Western blot and immunofluorescence. Compared with the blank control group, the model control group witnessed significantly increased mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1β and IL-18. As revealed by the comparison with the model control group, Huanglian Wendan Decoction could effectively regulate the obesity status, reduce body weight, correct the abnormal levels of 2-hour plasma glucose(2 hPG), insulin resistance index(IRI), insulin sensitivity index(ISI), and lower the mRNA and protein expression of NF-κB, NLRP3, caspase-1, IL-1β and IL-18 in the skeletal muscle tissue of IGT rats. Combined with previous studies, the above results showed that the occurrence and development of IGT was closely related to inflammatory response and the classic pyroptosis pathway in skeletal muscle, such as NLRP3/caspase-1/IL-1β, IL-18. It is inferred that the mechanism of Huanglian Wendan Decoction was to alleviate insulin resistance(IR) and then reverse the course of IGT lies in the regulation of the abnormal insulin receptor signaling pathway based on the NLRP3 inflammasome pathway.

Mechanism of Huanglian Wendan Decoction in intervening IGT IR based on liver cell pyroptosis / 中国中药杂志

To investigate the mechanism of Huanglian Wendan Decoction in intervening impaired glucose tolerance( IGT) rat insulin resistance( IR) based on the pyroptosis pathway of liver cells. The IGT rat model was established by high-fat diet( 20 weeks) combined with high temperature,humidity environment and inactive lifestyle. The experiment was divided into blank group,model group,metformin hydrochloride group( positive group)( 0. 05 g·kg~(-1)·d~(-1)) and Huanglian Wendan Decoction group( 7. 8 g·kg~(-1)·d~(-1)). After continuous intragastric administration for 4 weeks,the body weight,body length and abdominal circumferences of all the rats were measured,the Lee' s obesity indexes was calculated,and the levels of fasting plasma glucose( FPG) and 2-hour plasma glucose( 2 hPG) in each group were measured. Serum insulin levels( FINS) and tumour necrosis factor-α( TNF-α) levels were detected by ELISA,and insulin sensitivity index( ISI) and insulin resistance index( IRI) values were calculated. The expressions of cysteinyl aspartate specific proteinase-1( caspase-1),gasdermin D( GSDMD),interleukin-1β( IL-1β) and interleukin-18( IL-18) m RNA and proteins in liver tissues were detected by Real-time PCR and Western blot. Immunofluorescence was used to detect the expressions of caspase-1 and GSDMD protein in liver tissues. Huanglian Wendan Decoction could effectively reduce the weight of model rats,improve abdominal obesity,FINS,IRI and ISI indexes and correct 2 hPG levels. Compared with blank group,TNF-α levels in serum and caspase-1,GSDMD,IL-1β and IL-18 expressions in liver tissue of model control group were increased significantly. Huanglian Wendan Decoction could effectively reduce TNF-α level in serum,regulate the expressions of caspase-1,GSDMD,IL-1β and IL-18 genes and proteins in liver tissues of IGT rats. The above results showed that the occurrence and development of " obesity-IR-abnormal glucose metabolism-type 2 diabetes mellitus" was closely related to inflammatory response and the classical pyroptosis pathway mediated by caspase-1/GSDMD. The mechanism of Huanglian Wendan Decoction in improving IR may be correlated with reduction of the level of inflammatory factors and the alleviation of the state of pyroptosis,and thus reverse the course of IGT.

Effect of Huanglian Wendantang on Inflammatory Response and Hepatocyte Burn Death in IGT Rats / 中国实验方剂学杂志

Objective:To investigate whether there is inflammatory reaction and cell pyroptosis in impaired glucose tolerance （IGT） rats induced by high-fat diet and the intervention effect of Huanglian Wendantang. Method:Healthy male SD rats were fed with 45% fat content diet for 20 weeks to replicate the IGT model. The rats in line with the model establish criteria were randomly divided into 3 groups， with 10 rats in each group， another 10 rats were selected as the blank control group. Huanglian Wendantang group was given 7.8 g·kg^-1·d^-1 compound decoction of Huanglian Wendantang， and the positive control group was given 0.05 g·kg^-1·d^-1 aqueous solution of metformin hydrochloride， with the dose volume of 10 mL·kg^-1·d^-1. The blank group and the model group were given the same volume of distilled water. After continuous intragastric administration for 4 weeks， the body weight， body length and abdominal circumferences were measured， the Lee's obesity index was calculated， and the levels of fasting plasma glucose （FPG） and 2-hour plasma glucose （2 h PG） were detected in each group. Serum interleukin-6 （IL-6） content was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of nuclear factor kappa B （NF-<italic>κ</italic>B）， cysteinyl aspartate specific proteinase-1 （Caspase-1） and NOD-like receptor protein 3 （NLRP3） in liver tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Immunofluorescence was used to detect the expression of Caspase-1 and NLRP3 in rat liver. Hematoxylin and eosin （HE） staining was used to observe the morphology of liver tissue. Result:Compared with blank group， the body weight， abdominal circumference， body length and Lee's index in model group were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， the levels of FPG and 2 h PG were significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， serum IL-6 content and NF-<italic>κ</italic>B， Caspase-1 and NLRP3 gene and protein expressions in liver tissue were significantly increased （<italic>P</italic><0.01）， immunofluorescence technique showed that Caspase-1 and NLRP3 expressions increased obviously in IGT rat model’s liver tissues， and inflammatory cells infiltration was observed obviously in HE stained rat liver tissue model. Compared with model group， Huanglian Wendantang and metformin hydrochloride groups could effectively reduce the body weight of IGT rats （<italic>P</italic><0.01） and abdominal obesity， and correct the levels of FPG and 2 h PG （<italic>P</italic><0.01）， while effectively reducing serum IL-6 content and gene and protein expressions of NF-<italic>κ</italic>B， Caspase-1 and NLRP3 in liver tissues of IGT rats， and alleviating inflammatory cell infiltration. Conclusion:Inflammatory response exists in IGT model rats induced by high-fat diet. Huanglian Wendantang can obviously reduce its inflammatory response and alleviate liver cell pyroptosis.

Effect of Huanglian Wendantang on Classical Pathway of Skeletal Muscle Pyroptosis in IGT Rats / 中国实验方剂学杂志

Objective:To explore the effects of Huanglian Wendantang （HLWDT） on pyroptosis of skeletal muscle in rats with impaired glucose tolerance （IGT） and to explain the mechanism based on NOD-like receptor protein 3 （NLRP3）/cysteine aspartate-specific protease-1 （Caspase-1）/gasdermin D （GSDMD）/interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）/IL-18 signaling pathway. Method:The SD male rats were fed with 45% high-fat diet for 20 weeks to induce the IGT model. After modeling， the rats were randomly divided into a blank group， a model group， a positive control group （metformin hydrochloride， 0.05 g·kg^-1d^-1）， and an HLWDT （7.8 g·kg^-1d^-1） group based on the body weight of rats. The blank group and the model group were fed with the same volume of distilled water. The dose for each group was set as 10 mL·kg^-1d^-1. After four weeks of continuous gavage， blood was collected and serum was separated. The skeletal muscles of rats were stored in liquid nitrogen. Subsequently， serum IL-1<italic>β</italic> and IL-18 were detected by the enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of NLRP3， Caspase-1， and GSDMD were detected by real-time quantitative PCR （Real-time PCR） and Western blot， respectively. The expression of GSDMD， IL-1<italic>β</italic>， and IL-18 proteins in skeletal muscle tissues was detected by immunofluorescence. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of skeletal muscles. Result:Compared with the blank group， the model group showed increased IL-1<italic>β</italic> and IL-18 in serum， and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （<italic>P</italic><0.01）. Immunofluorescence assay showed that GSDMD， IL-18， and IL-1<italic>β </italic>protein expression in skeletal muscle tissues of the model group was significantly elevated （<italic>P</italic><0.01）. HE staining showed obvious pathological changes in skeletal muscles. Compared with the model group， the HLWDT group and the positive control group could decrease IL-1<italic>β</italic> and IL-18 in serum and NLRP3， Caspase-1， and GSDMD gene and protein expression in skeletal muscle tissues （<italic>P</italic><0.01）. In addition， immunofluorescence assay revealed that HLWDT could reduce protein expression levels of GSDMD， IL-1<italic>β</italic>， and IL-18 in skeletal muscles of IGT rats （<italic>P</italic><0.01）. The results of HE staining showed that HLWDT could improve the pathological changes of skeletal muscles in IGT rats<bold>.</bold> Conclusion:HLWDT can inhibit skeletal muscle pyroptosis of IGT rats， and the mechanism may be closely related to NLRP3/Caspase-1/GSDMD/IL-18/IL-1<italic>β</italic> signaling pathway.

Effects of pioglitazone on visceral fat metabolic activity in patients with type 2 diabetes mellitus or impaired glucose tolerance / 中国糖尿病杂志

Objective To study the effects of pioglitazone on visceral fat tissue metabolic activity in patients with type 2 diabetes mellitus or impaired glucose tolerance by using 18 fluoro deoxy glucose (FDG)‐positron emission tomography (PET)andcomputed tomography (CT)imaging. Methods FDG‐PET and CT imaging were performed in 62 patients with type 2 diabetes mellitus (T2DM ) or impaired glucose tolerance (IGT ). Lipid and glycemic profiles and inflammatory markers were detected in all patients. These patients randomly received treatments with either pioglitazone or glimepiride for 16 weeks.Results After 16 weeks ,pioglitazone‐treated group versus glimepiride‐treated group showed a significantly decreased visceral fat area[(109.1 ± 45.0) vs(122.5 ± 52.0 )cm2 ] and a significantly decreased visceral fat metabolic activity[(0.47 ± 0.11)vs(0.55 ± 0.11)](P<0.05). Conclusion Our study indicates that pioglitazone decreases the visceral fat volume and its metabolic activity in patients with T 2DM or IGT.

Pharmacological intervention of IGT / 中国糖尿病杂志

[Summary] There is a huge population of adults with pre-diabetes in China ,and the majority of whom are impaired glucose tolerance(IGT) patients. IGT is not only a risk factor for type 2 diabetes ,but is also closely related to diabetic microvascular and macrovascular complications. Preventing or delaying the development of diabetes by intervention on IGT has become imperative. When lifestyle intervention alone cannot achieve the ideal goal of diabetes prevention ,pharmacological intervention should be considered. This review will discuss thepathophysiology of IGT ,and the effectiveness ,safety and pharmacoeconomics of IGT pharmacological intervention.

Efficacy of Acarbose in combination with life style modification on waist circumference in patients with impaired glucose tolerance / 中国糖尿病杂志

Objective To investigate the effect of acarbose on waist circumference (WC) in patients with IGR. Methods A total of 46 subjects with IGT (2 hPG>7.8 mmol/L) were selected in this study. All the subjects were given diet and exercise treatment for half a month and then treated with acarbose for 3 months in combination with life style modification. Self-paired method was adopted to compare islet βcell function and WC before and after the treatment. Results After acarbose treatment for 3 months ,islet βcell function were markedly improved. Insulin secretion of Fins and 2 hIns decreased ,early insulin secretion index (ΔI30/ΔG30 ) significantly increased ,and BMI and WC were reduced significantly (P<0.05) . Multiple regression analysis showed that there was correlation between WC and TG ,insulin resistance index (HOMA-IR) and islet β-cell function index (HOMA-β) (P< 0.05). Conclusion Acarbose in combination with life style modification can improve islet β-cell function in patients with IGR and reduce WC and abdominal fat accumulation as well.

Impaired glucose tolerance: A pilot study in randomly selected population of Chennai.

Impaired glucose tolerance (IGT) is considered as a prediabetic state that occupies a grey area between Diabetes mellitus (DM) and normal glucose tolerance (NGT). If diabetes is detected at the stage of impaired glucose tolerance, it may be possible to halt the progression to overt diabetes. The study was conducted to assess the prevalence of impaired glucose tolerance and its relation with age, sex, body mass index (BMI), waist-hip ratio (WHR) and family history of diabetes mellitus in a randomly selected Chennai population of 200 subjects of both sexes as per the inclusion and exclusion criteria. Blood glucose concentration, body mass index and waist-hip ratio were measured by approved methods. All the data were statistically analyzed. Prevalence of IGT in this study population is 8.5%. BMI and family history of diabetes showed association with IGT. WHR showed association with IGT in males, but not in females. The prevalence of IGT is similar with differing age groups and sex.

Clinical Significance of Fasting Glucose Criteria in Metabolic Syndrome

Both Adult Treatment Panel III(ATP III) and International diabetes Federation(IDF) adopted impaired fasting glucose (IFG) as one of the criteria for identifying individuals with metabolic syndrome. However, many studies have shown that IGT is a better predictor of cardiovascular disease(CVD) than IFG. Recently the American Diabetes Association(ADA) revised the diagnostic criteria for IFG, lowering the diagnostic threshold from 110 mg/dL to 100 mg/dL to improve the alignment of IFG and IGT. Although the revised definition of IFG increases the prevalence of metabolic syndrome as well as that of IFG, relative risk of CVD is still lower than that of IGT. The clinical and public health implications of the revised IFG definition remain to be elucidated.

Therapeutic effect of Xiaoke Huayu tablet on impaired glucose tolerance / 解放军医学杂志

Objective To evaluate the therapeutic effect of Xiaoke Huayu tablet on impaired glucose tolerance (IGT). Methods 168 patients who were proved to have IGT were randomly divided into two groups: treatment group (n=86) and control group (n=82). All the patients were asked to take abstinent diet with proper athletic exercises. The patients in the treatment group were treated with Xiaoke Huayu tablet. No drug was given to patients of the control group. The therapeutic effect and data of laboratory findings before and after treatment in both groups were analyzed and compared. Results There was significant differences before and after treatment between two groups. The total effective rate was 91.8% in the treatment group and 68.3% in the control group (P

Clinical Observation on the Effect of Wentang Granule for Impaired Glucose Tolerance——A Report of 48 Cases / 中医杂志

Objective To study the effect of Wentang Granule(Granule for Stabilizing Glucose) on impaired glucose tolerance(IGT) of type Ⅱ diabetes.Methods Totally 150 patients with diagnosis of IGT were randomly divided into 3 groups:education group,observation group,and control group,with 50 cases in each.They were treated with guidance on life style,Wentang Granule,and Acarbose respectively and observed for 2 years.The observed indexes included fasting blood glucose(FBG),serum lipid,body mass index(BMI),waist hip ratio(WHR),changes of TCM symptoms and scores.The therapeutic effect was evaluated with the changes of glucose tolerance.Results After treatment,the conversion rate of normal glucose tolerance and diabetes of the observation group and control groups was significantly different from that of the education group(P