High fat diet- induced obesity decreases ErbB receptors expression in liver and adipose tissue in C57BL/6 mice

Neuregulins (NRGs) are a family of signaling proteins that bind to receptor tyrosine kinases of the ErbB family (ErbB2 to ErbB4), which can homo- or heterodimerize depending on their structural features and cell type. Many studies have proposed that decreased NRG levels are a common characteristic of obesity. In liver and adipose tissue, the increase in NRG expression has protective effects against obesity. However, it is still unknown whether ErbBs expression is altered in this pathology. We hypothesized that high fat diet-induced obesity downregulates ErbB receptors expression in obese mice compared to normal weight mice. Males C57BL/6 mice (n=6-7 for each group) were fed for 12 weeks and divided into: (i) control diet (CD; 10%-kcal fat, 20%-kcal protein, 70%-kcal carbohydrates), and (ii) high fat diet (HFD; 60%-kcal fat, 20%-kcal protein, 20%-kcal carbohydrates). General parameters and ErbBs expression (qPCR, immunohistochemistry and Western blot) were evaluated. We observed a significant increase in final body weight (47%), adipose tissue to body weight ratio (244%) and HOMA-IR (69%), among other parameters, in obese mice. In HFD group significantly decreased ErbB2 (48%) and ErbB3 (66%) mRNA levels in liver (no change in ErbB4), and ErbB2 (43%), ErbB3 (76%) and ErbB4 (35%) in adipose tissue, compared to CD. Furthermore, ErbB2 and ErbB3 protein levels decreased significantly in HFD group compared to the CD in liver. Therefore, our results suggest that HFD-induced obesity significantly decreases ErbBs expression in liver and adipose tissue in this murine model, that may be associated with alterations in the NRG pathway in obese mice.

Las neuregulinas (NRGs) son una familia de proteínas de señalización que se unen a receptores tirosina quinasas de la familia ErbB (ErbB2 a ErbB4), que pueden homo- o heterodimerizar dependiendo de sus características estructurales y del tipo celular. Estudios han propuesto que la disminución de los niveles de NRG es una característica común de la obesidad. En el hígado y el tejido adiposo (TA), el aumento de la expresión de NRG tiene efectos protectores contra la obesidad. Sin embargo, aún se desconoce si la expresión de ErbBs está alterada en esta patología. Nuestra hipótesis es que la obesidad inducida por una dieta alta en grasas (DAG) disminuye la expresión de los ErbB en ratones obesos. Ratones machos C57BL/6 (n=6-7 para c/grupo) fueron alimentados durante 12 semanas y divididos en: (i) dieta control (DC; 10%-kcal grasa, 20%-kcal proteína, 70%-kcal carbohidratos), y (ii) DAG (60%-kcal grasa, 20%-kcal proteína, 20%-kcal carbohidratos). Se evaluaron los parámetros generales y la expresión de ErbBs (qPCR, inmunohistoquímica y Western blot). Observamos un aumento significativo del peso corporal final (47%), de la relación tejido adiposo/peso corporal (244%) y del HOMA-IR (69%), entre otros parámetros, en ratones obesos. En este grupo disminuyó significativamente los niveles de ARNm de ErbB2 (48%) y ErbB3 (66%) en el hígado (sin cambios en ErbB4), y de ErbB2 (43%), ErbB3 (76%) y ErbB4 (35%) en el TA. Además, los niveles de proteína ErbB2 y ErbB3 disminuyeron significativamente, en comparación con el grupo DC en el hígado. Nuestros resultados sugieren que la obesidad inducida por DAG disminuye significativamente la expresión de ErbBs en el hígado y el TA, que puede estar asociado con alteraciones en la vía NRG en ratones obesos.

Falciparum malaria is associated with risk markers of type 2 diabetes mellitus in individuals with or without COVID-19 exposure

Background: Scientific information on the impact of malaria on the risk of developing type 2 diabetes mellitus (T2DM) after recovery from the coronavirus disease 2019 (COVID-19) is limited in the Ghanaian context. The purpose of this study was to examine the association between selected risk markers of T2DM in falciparum malaria patients post-COVID-19 or not at a tertiary hospital in Ghana. Methodology: This was a descriptive cross-sectional comparative study of 38-recovered COVID-19 adult participants with malaria and 40 unexposed COVID-19 adults with malaria at the Tamale Teaching Hospital, Ghana. Demographic, anthropometric and levels of glucose, insulin, C-reactive protein and lipid profiles were measured in the two groups of participants under fasting conditions. Parasitaemia was assessed microscopically but insulin resistance and beta-cell function were assessed by the homeostatic model. Results: The COVID-19 exposed participants were older (p=0.035) with lower parasitaemia (p=0.025) but higher mean levels of insulin, insulin resistance, and beta-cell function compared with their unexposed counterparts (p<0.05). Parasitaemia correlated positively with a number of the measured indices of diabetogenic risk markers in the COVID-19 exposed group only, and predicted (Adjusted R2=0.751; p=0.031) by beta-cell function, C-reactive protein and triglycerides with the model explaining about 75% of the observed variation. Parasitaemia could only be predicted (Adjusted R2=0.245; p=0.002) by C-reactive protein with the model explaining just about a quarter of the observed variation in the COVID-19 unexposed group. Insulin resistance and sub-optimal beta-cell function were detected in both groups of participants. Conclusion: Falciparum malaria is associated with risk markers for development of T2DM irrespective of COVID-19 exposure. Insulin resistance, inflammation and sub-optimal beta-cell secretory function may drive the risk. The observed diabetogenic risk is higher in the recovered COVID-19 participants.

Relationship between new surrogate marks of insulin resistance and bone mineral content in adolescents / 中国学校卫生

Objective@#To analyze the relationship between new surrogate marks of insulin resistance (IR) and bone mineral content (BMC) in adolescents, and predictive value of the new surrogate marks on low bone mass, so as to provide scientific basis for early identification and prevention of skeletal related diseases in adolescents.@*Methods@#A total of 1 594 adolescents aged 12-18 years in Yinchuan City were selected by convenience sampling and stratified cluster random sampling from September 2017 to September 2020, and triglyceride and glucose index (TyG), triglyceride glucose-body mass index (TyG-BMI) and triglyceride/high density lipoprotein cholesterol (TG/HDL-C) were calculated as new simplified IR index. The correlation between different simplified IR indexes and BMC level was analyzed by partial correlation. Binary Logistic regression was used to analyze the relationship between IR index and low bone mass, and receiver operating characteristic (ROC) curve was constructed to analyze its evaluation effect on low bone mass.@*Results@#After adjusting for confounding factors such as gender, age, smoking, drinking, family history of hypertension, systolic blood pressure (SBP) and diastolic blood pressure (DBP), the new surrogate marks of IR were positively correlated with BMC level (TyG: r =0.11, TyG-BMI: r =0.58, TG/HDL-C: r =0.21, P <0.01). After further adjustment of body mass index (BMI), fat mass (FM) and lean mass (LM), the relationship between IR indexes and BMC turned into negative correlation (TyG: r =-0.20, TyG-BMI: r =-0.18, TG/HDL-C: r=-0.14, P <0.01). After adjusting for confounding factors such as gender, age, smoking, drinking, family history of hypertension, SBP and DBP, Logistic regression results showed that the increase of TyG, TyG-BMI and TG/HDL-C levels reduced the possibility of low bone mass in adolescents (TyG: OR=0.63, 95%CI = 0.40-0.98, TyG-BMI: OR=0.94, 95%CI =0.93-0.96, TG/HDL-C: OR=0.31, 95%CI=0.17-0.58, P <0.01). After adjusting BMI, FM and LM, the above results were completely reversed. Girls with high TyG and TG/HDL-C levels were 4.95 and 4.38 times more likely to have low bone mass than those with low TyG and TG/HDL-C levels (TyG: OR=4.95, 95%CI =1.29- 18.95 , TG/HDL-C: OR=4.38, 95%CI=1.04-18.50, P <0.05). ROC curve showed that TyG-BMI had the best predictive value on low bone mass (AUC=0.80, 95% CI=0.77-0.83, P <0.01).@*Conclusion@#The new surrogate marks of IR in adolescents are negatively correlated with adolescent BMC, of which TyG-BMI is the best for assessing of low bone mass and can serving as a reliable indicator for early identification of low bone mass.

Comparison of the predictive value of new simplified insulin resistance assessment indexes in identifying left ventricular subclinical dysfunction in T2DM patients / 解放军医学杂志

Objective To investigate the predictive value of new simplified insulin resistance(IR)assessment indexes in identifying subclinical left ventricular systolic function impairment in patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 T2DM patients with preserved left ventricular ejection fraction(LVEF≥50%)who were admitted to Department of Endocrinology of the First Affiliated Hospital of Air Force Medical University from June 2021 to December 2021 were retrospectively analyzed.All patients underwent two-dimensional speckle tracking echocardiography to measure left ventricular global longitudinal strain(GLS).According to GLS value,the subjects were divided into the normal group(GLS≥18%group,n=80)and the impaired group(GLS<18%group,n=70).Some new simplified IR assessment indicators were calculated and compared between the two groups,including body mass index(BMI),TG/HDL-C ratio,triglyceride-glucose(TyG)index,TyG-BMI index,TyG-WHR and metabolic score for IR(METS-IR).Correlation between the GLS and the new simplified IR assessment indexes was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of different simplified IR assessment indexes,with the area under the curve(AUC)calculated.Furthermore,according to whether the subjects were complicated with hypertension,binary logistics regression analysis was performed to explore the independent correlation between the simplified IR assessment index and GLS<18%.Results Total 150 were included with aged(54.5±13.7)years with 96(64.0%)men and 54(36.0%)women.Compared with the GLS≥18%group,the TG/HDL-C ratio,TyG index,TyG-BMI,and METS-IR of subjects in the GLS<18%group were significantly increased(P<0.05).Pearson correlation analysis showed that TG/HDL-C ratio,TyG index,TyG-BMI,TyG-WHR,and METS-IR were negatively correlated with GLS(P<0.05).ROC analysis showed that TyG index had a certain predictive value for the evaluation of GLS<18%(AUC=0.678,95%CI 0.591-0.765,P<0.001).Stratification based on hypertension and further adjusting for confounding factors,TyG index remains significantly associated with GLS<18%(OR=3.249,95%CI 1.045-10.103,P=0.042).Conclusions The novel simplified insulin resistance evaluation indexes are closely associated with left ventricular subclinical systolic dysfunction in T2DM patients with preserved ejection fraction.TyG index is an effective index to identify left ventricular subclinical dysfunction in these populations.

Research Progress of miRNA in Non-alcoholic Fatty Liver Disease / 昆明医科大学学报

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,with a global prevalence of approximately 30.05% to 32.4% .It is closely associated with various other diseases.In recent years,microRNAs(miRNAs)have played a crucial role as non-invasive biomarkers in understanding the pathogenesis and diagnosis of NAFLD.miRNAs play significant roles in both lipid metabolism and insulin resistance,exerting specific regulatory functions in the development and progression of NAFLD.miRNAs are small RNA molecules that regulate the gene expression and protein synthesis by controlling the transcription and translation of target genes.This article provides a comprehensive overview of the roles and mechanisms of miRNAs in lipid metabolism,insulin resistance,and the occurrence and development of NAFLD.

Effects of intraoperative blood glucose fluctuation and postoperative insulin resistance on cognitive dyfunction in elderly patients after thoracoscopic radical resection of lung cancer under general anesthesia / 天津医药

Objective To analyze the influence of intraoperative blood glucose fluctuation and postoperative insulin resistance(IR)on postoperative cognitive dyfunction(POCD)in elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia.Methods A total of 352 elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia were collected and divided into the POCD group(n=84)and the non-POCD group(n=268).The covariates between the two groups were balanced by propensity score matching method(PSM).Eighty-four cases in each group were successfully matched.The data between the two groups before and after PSM were compared.After PSM,receiver operating characteristic(ROC)curve of blood glucose fluctuation amplitude for predicting POCD was drawn,and patients were divided into the low-level blood glucose fluctuation group(n=97)and the high-level blood glucose fluctuation group(n=71)according to the cut-off value.According to the existence of postoperative IR,patients were divided into the IR group(n=53)and the non-IR group(n=115).Then,incidences of POCD between groups were compared.Logistic regression was used to analyze the influencing factors of POCD.Results Before PSM,the POCD group had older age,higher blood glucose fluctuation amplitude,IR ratio,operation time,anesthesia time,propofol dosage,remifentanil dosage and sufentanil dosage in anesthesia maintenance period than those in the non-POCD group(P＜0.05).The POCD group had higher blood glucose fluctuation amplitude and IR ratio than those in the non-POCD group after PSM(P＜0.05).After PSM,the incidences of POCD in the high-level blood glucose fluctuation group and the IR group were higher than those in the low-level blood glucose fluctuation group and the non-IR group(P＜0.05).Logistic regression analysis showed that higher intraoperative blood glucose fluctuation(OR=9.140,95%CI:4.338-19.257)and postoperative IR(OR=4.034,95%CI:1.163-13.991)were risk factors of POCD.Conclusion The risk of POCD in elderly patients undergoing thoracoscopic radical lung cancer surgery under general anesthesia is increased in patients with higher intraoperative blood glucose fluctuation and postoperative IR.

MiRNA-122 contributes to the effect of exercise on non-alcoholic fatty liver / 中国组织工程研究

BACKGROUND:In recent years,with the improvement of living standards,non-alcoholic fatty liver disease has a gradually increasing trend.miRNA-122 is one of the most abundant microRNAs in the liver,which plays an important role in maintaining the environmental stability and differentiation of the liver.Exercise training is a non-drug treatment for non-alcoholic fatty liver disease,which may improve liver lipid metabolism by regulating the expression of miRNA-122. OBJECTIVE:To review the effects of miRNA-122 on the pathological factors related to non-alcoholic fatty liver disease as well as the effects of exercise on the expression of miRNA-122 and the occurrence and development of nonalcoholic fatty liver disease. METHODS:The first author searched the databases of CNKI,WanFang,VIP,PubMed,Geenmedical,EBSCO,Medline,Web of Science,and Elsevier using"non-alcoholic fatty liver disease,microRNA,microRNA-122,lipid metabolism,inflammatory response,insulin resistance,exercise,physical exercise,exercise training"as the English and Chinese search terms for all relevant literature published before June 5,2022.All included documents were screened,summarized,and analyzed.Finally,68 documents were included for review. RESULTS AND CONCLUSION:Compared with the healthy control group,the expression of circulating miRNA-122 is increased in patients with non-alcoholic fatty liver disease.The level of miRNA-122 may show different expression levels at different stages of non-alcoholic fatty liver disease.miRNA-122 can regulate the expression of downstream-related proteins,influence lipid metabolism,inflammatory response,insulin resistance and other pathogenic factors in non-alcoholic fatty liver disease by targeting base complementary pairing sites on mRNA or directly acting as physiological ligands of some RNA receptors.Different exercise modes can improve non-alcoholic fatty liver disease.Therefore,patients with non-alcoholic fatty liver disease need to complete at least 120 minutes of moderate-intensity exercise every week to have a positive effect.For patients who can tolerate various exercises,priority should be given to the combination of aerobic and resistance exercises 4-5 times a week.The exercise intensity should be 50%-70%of the maximum heart rate and the exercise should last for>3 months.For patients with poor tolerance,resistance exercise may be more feasible than aerobic exercise.In addition,patients with non-alcoholic fatty liver disease can also choose proper exercise modes according to their own disease conditions(such as liver enzymes and lipid levels).Exercise can be used as a feasible strategy to prevent non-alcoholic fatty liver disease,reduce liver steatosis,and alleviate liver inflammatory response and insulin resistance.Exercise training can regulate the expression of miRNA-122,but in patients with non-alcoholic fatty liver disease,the effect of exercise on miRNA-122 and its related signal pathways remains to be studied.

Mechanism by which static exercise improves insulin resistance in skeletal muscle of type 2 diabetes / 中国组织工程研究

BACKGROUND:Skeletal muscle insulin resistance is the key pathological link of type 2 diabetes.Static exercise can effectively improve skeletal muscle insulin resistance,but the mechanism remains unclear. OBJECTIVE:To explore the mechanism of static exercise on insulin resistance in the skeletal muscle of type 2 diabetic mice based on the phosphatidyl inositol 3-kinase(PI3K)/protein kinase B(AKT)/glucose transporter(GLUT4)signaling pathway. METHODS:After 1 week of adaptive feeding,7 out of 40 C57BL/6 mice were randomly selected as blank group and fed common diet,while the other mice were fed high-fat diet and taken to prepare type 2 diabetes models through the low-dose streptozotocin intraperitoneal injection.Twenty-four mice were successfully modeled and they were randomly divided into model group(n=8),metformin group(n=8)and static exercise group(n=8),which continued to be fed high-fat diet.The metformin group was given 200 mg/kg metformin dissolved in normal saline(2 ml/kg)by gavage,once a day,for 6 weeks.The static exercise group was given normal saline daily by gavage and carried out static exercise,30 minutes a day,6 days per week.The model group was given the same dose of normal saline daily by gavage without exercise intervention.After the intervention,the fasting blood glucose of each group was detected,the intraperitoneal glucose tolerance test was performed,and the area under the glycemic curve was calculated.Glycosylated hemoglobin,serum insulin,insulin resistance index were detected by ELISA.Total cholesterol,triglyceride,high-density lipoprotein,low-density lipoprotein were detected using biochemical methods.The mRNA expression levels of PI3K,AKT and GLUT4 in the gastrocnemius of mice were detected by real-time quantitative PCR.Morphological changes of the gastrocnemius were observed by hematoxylin-eosin staining,and the cross-sectional area of muscle fibers was calculated. RESULTS AND CONCLUSION:Compared with the blank group,fasting blood glucose,glycosylated hemoglobin,area under the glycemic curve,insulin resistance index,total cholesterol,triglyceride and low-density lipoprotein levels were significantly increased in the model group(P<0.01,P<0.05).Whereas,these indicators were significantly lower in the static exercise and metformin group than the model group(P<0.01,P<0.05).Compared with the blank group,serum insulin and high-density lipoprotein levels were significantly declined in the model group(P<0.01)and the mRNA expression of PI3K,AKT and GLUT4 in the gastrocnemius of mice were also significantly reduced(P<0.01).These indicators were significantly elevated in the metformin group and static exercise group compared with the blank group(P<0.01).Compared with the blank group,the muscle fibers in the model group were disordered,and the muscle cells atrophied and the muscle fiber gap widened.The cross-sectional area of muscle fibers was significantly decreased in the model group compared with the blank group(P<0.01).Compared with the model group,atrophy of the gastrocnemius fibers and muscle fiber space were improved in the static exercise group and the metformin group,and the cross-sectional area of muscle fiber was significantly increased in both groups(P<0.01).These findings indicate that static resistance training may promote glucose uptake and utilization by up-regulating the expression of PI3K,AKT and GLUT4 mRNA in skeletal muscle tissue,thereby improving the morphology and function of skeletal muscle tissue,alleviating insulin resistance and regulating glucose homeostasis.

Effects of high-intensity interval training and moderate-intensity continuous training on body composition and glucose metabolism in overweight or obese patients with type 2 diabetes:a Meta-analysis / 中国组织工程研究

OBJECTIVE:To systematically evaluate the effects of high-intensity interval training(HIIT)and moderate-intensity continuous training(MICT)on body composition and glucose metabolism-related indexes in overweight or obese patients with type 2 diabetes and to compare the improvement effect of the two exercise modalities,thereby providing a reference basis for the development of exercise prescription for overweight or obese patients with type 2 diabetes. METHODS:The Cochrane Library,PubMed,EMbase,Web of Science,CNKI,CBM,WanFang,and ClinicalTrials.gov were searched for randomized controlled trials comparing the effects of HIIT and MICT interventions on body composition and glucose metabolism-related indicators in overweight or obese patients with type 2 diabetes.The search was conducted from database inception to June 2022.Meta-analysis of outcome indicators was performed using RevMan 5.4. RESULTS:(1)A total of 13 randomized controlled trials with 371 subjects were included,and the overall quality of the included studies was relatively high.(2)There was no significant difference in the improvement of body composition between HIIT and MICT[body mass:weighted mean difference(WMD)=2.44,95%confidence interval(CI):-3.01-7.89,P＞0.05;body mass index:WMD=0.28,95%CI:-1.21-1.77,P＞0.05;waist circumference:WMD=2.16,95%CI:-2.04-6.35,P＞0.05;body fat percentage:WMD=0.47,95%CI:-2.11-3.05,P＞0.05).(3)The results of subgroup analysis showed that there was a significant difference in body mass and body mass index between the"training cycle≥12 weeks"subgroup and the"training frequency≤3 times/week"subgroup(training cycle≥12 weeks subgroup:WMD=4.25,95%CI:0.90-7.59,P=0.01;WMD=2.71,95%CI:1.92-3.51,P＜0.000 01;training frequency≤3 times/week subgroup:WMD=5.14,95%CI:1.7-8.57,P=0.003;WMD=1.67,95%CI:0.66-2.67,P=0.001).(4)The results of sensitivity analysis showed that there was a significant difference in body fat percentage between the HIIT and MICT groups(WMD=2.17,95%CI:1.20-3.14,P＜0.000 1),while there was no significant difference in the improvement of glucose metabolism between the HIIT and MICT groups(fasting blood glucose:WMD=0.31,95%CI:-0.17-0.79,P＞0.05;glycosylated hemoglobin:WMD=0.01,95%CI:-0.19-0.20,P＞0.05;insulin resistance index:WMD=-0.14,95%CI:-0.71-0.42,P＞0.05).(5)The results of subgroup analysis showed that fasting blood glucose was significantly different in the subgroup of"training frequency≤3 times/week"(WMD=0.92,95%CI:0.25-1.60,P=0.007)and glycosylated hemoglobin was significantly different in the"training frequency＞3 times/week"subgroup(WMD=-0.2,95%CI:-0.3 to-0.1,P＜0.000 1). CONCLUSION:Overall,there is no significant difference between HIIT and MICT in improving body composition such as body mass,body mass index,waist circumference,body fat percentage as well as improving glucose metabolic indexes such as fasting blood glucose,glycated hemoglobin and insulin resistance index in overweight or obese patients with type 2 diabetes.When the training period is≥12 weeks and the training frequency is≤3 times/week,MICT has a better effect on the improvement of body mass as well as body mass index.

Effects of cumulative and continuous exercise of different intensities on intestinal mucosal permeability in insulin-resistant mice / 中国组织工程研究

BACKGROUND:The relationship between insulin resistance and intestinal mucosal permeability may be related to excess fat,inflammation and oxidative stress.At present,the influence of different kinds of exercise on this relationship has not been fully studied,and the relevant mechanism needs to be further studied. OBJECTIVE:To study the effects of continuous exercise and cumulative exercise on intestinal mucosal permeability of insulin-resistant mice induced by high fat diet,and to compare the effects of different intensities of exercise,thereby evaluating the health-promoting effects of cumulative exercise. METHODS:Four-week-old male C57BL/6J mice were fed high-fat diet to induce insulin resistance,and mice with successful modeling were randomly divided into five groups:high-fat insulin resistance group,general dietary insulin resistance group,moderate-intensity continuous exercise group,moderate-intensity cumulative exercise group,and high-intensity cumulative exercise group.Mice in the high-fat insulin resistance group received high-fat diet and mice in the other groups were fed normally.All the exercise groups received 8 weeks of different forms of treadmill training.Mice in the moderate-intensity sustained exercise group exercised for 50 minutes at a speed of 11 m/min.Mice in the moderate-intensity cumulative exercise group were subjected to 12.5 minutes of exercise,four times a day(3 hours between sessions),at a speed of 11 m/min.Mice in the high-intensity cumulative exercise group exercised for 7.5 minutes once,four times a day(3 hours between sessions),at a speed of 19 m/min.At 48 hours after the final session,the levels of lipopolysaccharide and D-lactic acid in serum of mice were detected,the pathological changes of ileal tissue were observed by hematoxylin-eosin staining,and the expression of intestinal compact linking protein was detected by western blot.The expression of interleukin-10,tumor necrosis factor αin blood and ileum and intestinal secreted immunoglobulin A were detected by ELISA. RESULTS AND CONCLUSION:High-fat diet-induced insulin resistance was associated with body mass gain.The serum levels of endotoxin and D-lactic acid significantly increased,and the levels of tumor necrosis factor-α in serum and small intestine were significantly increased.Long-term regular cumulative exercise and continuous exercise could reduce the body mass of insulin-resistant mice,significantly improve glucose metabolism,and correct or improve insulin resistance symptoms.Both long-term regular cumulative exercise and continuous exercise could increase the expression of zonula occludens protein 1 and increase the secretion of secreted immunoglobulin A in intestinal mucosal tissue,thereby improving intestinal mucosal permeability,enhancing intestinal immune function,reducing the content of lipopolysaccharide in serum,and reducing the expression of pro-inflammatory factors in circulating blood and intestinal tissue.Finally,it could protect the intestinal mucosal barrier of insulin-resistant mice.Compared with medium-intensity cumulative exercise and continuous exercise,high-intensity cumulative exercise had more obvious effects on reducing body mass,improving insulin resistance symptoms and protecting intestinal mucosal barrier in insulin-resistant mice.

Effect of vitamin D on the structure and diversity of intestinal flora in spontaneously diabetic rats / 中国比较医学杂志

Objective To investigate the effect of vitamin D(VD)on intestinal flora in spontaneously diabetic rats.Methods Zucker diabetic fatty rats(ZDF rats)were randomised to control(Con)group,VD control(VD)group,model(T2DM)group,and VD intervention(VD+T2DM)group.Fasting blood glucose profiles and oral glucose tolerance levels were determined in rats of each group.16S rDNA sequencing was used to assess changes in rat intestinal flora.OTU analysis(Venn diagram),α diversity analysis(chao1,observed species,PD whole tree,and shannon and simpson),βdiversity analysis(principal coordinate analysis(PCoA)),flora structure,and colony species variability analysis(linear discriminant analysis and influence factor(LEfSe)analysis)were also performed.Results VD intervention significantly improved fasting blood glucose levels and insulin resistance in T2DM rats(P＜0.05).α diversity showed no significant differences in chao1,observed species,PD whole tree,and shannon and simpson indices between T2DM and VD+T2DM groups(P＞0.05).β diversity analysis showed that the VD+T2DM group had more species similarity to the Con group than the T2DM group.The dominant bacteria of rat intestinal flora in each group were significantly different.In comparison to the T2DM group,the VD+T2DM group showed a decrease in abundance of Bacteroidetes and increases in abundances of Firmicutes and Clostridium XIVa.Conclusions VD improves fasting glucose elevation and insulin resistance in T2DM rats.VD improves the structure of intestinal flora,decreases Bacteroidetes,and elevates Firmicutes and Clostridium XIVa abundances in T2DM rats.

Diagnostic value of quantitative analysis of skeletal muscle fat on insulin resistance in type 2 diabetes mellitus / 中国糖尿病杂志

Objective To explore the correlation between skeletal muscle fat content and insulin resistance(IR)in patients with type 2 diabetes mellitus(T2DM),and to evaluate the diagnostic value of skeletal muscle fat quantitative parameters for IR.Methods During January 2018 to January 2021,150 T2DM patients as observation group(T2DM group)and 100 healthy subjects as control group(NC group)were selected.All subjects underwent magnetic resonance imaging quantitatively analyzed skeletal muscle fat content,including intermuscular fat(IMAT),adipose tissue beneath fascia(SFAT)and subcutaneous fat(SCAT).Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of skeletal muscle fat quantitative parameters for IR in T2DM patients.Results The levels of IMAT and SFAT were higher in T2DM group than those in NC group[(10.05±1.34)%vs(7.16±2.06)%,(3.64±0.54)%vs(3.40±0.75)%,P<0.05],while the level of SCAT was lower than in T2DM group than in NC group[(20.16±6.34)%vs(24.97±6.57)%,P<0.05].Pearson correlation analysis showed that IMAT and SFAT were positively correlated with HbA1c and HOMA-IR(P<0.05),while SCAT was negatively correlated with HbA1c and HOMA-IR(P<0.05).ROC curve analysis showed that the area under the curve of IMAT,SFAT,and SCAT for the diagnostic value of T2DM combined with IR were 0.716,0.667 and 0.736,with sensitivities of 75.4%,72.9%and 76.4%,and specificity of 71.4%,65.2%and 68.1%.Conclusion Skeletal muscle fat contentis associated with IR.The quantitative parameters of skeletal muscle fat have good diagnostic efficacy for T2DM complicated with IR.

Changes of circulating Ectodysplasin A levels and its analysis of influencing factors in polycystic ovary syndrome / 中国糖尿病杂志

Objective To investigate the serum Ectodysplasin A(EDA)levels in women with polycystic ovary syndrome(PCOS)and explore the correlation of EDA and insulin resistance(IR).Methods A total of 256 newly diagnosed PCOS patients in Guangzhou First People's Hospital from September 2020 to September 2022 were selected.Taking BMI=25 kg/m2 as the cut-off point,the patients with PCOS were divided into obese subgroup(n=143)and non-obese subgroup(n=113).Among them,43 PCOS received six months of Liraglutide intervention.123 healthy women were normal control group(NC),which were divided into healthy obese subgroup(n=10)and healthy non-obese subgroup(n=113).Serum EDA and related biochemical indexes were detected in both groups.The correlation between serum EDA and metabolic index were analyzed.Results The serum EDA level in PCOS group was higher than that in NC group[(272.59±68.52)vs(214.51±61.36)pg/ml,P<0.05].Serum EDA in obese subgroup was higher than that in no-obese subgroup in PCOS patients[(301.11±55.81)vs(236.84±66.25)pg/ml,P<0.01].After the intervention of Liraglutide,serum EDA in PCOS women markedly decreased[(294.71±57.81)vs(336.0±61.23)pg/ml,P<0.05].EDA levels were correlated positively with body mass index(BMI),waist hip ratio(WHR),fasting blood glucose(FPG),2 hPG,fasting insulin,2 hIns,homeostasis model assessment for insulin resistance(HOMA-IR),TC,LDL-C and testosterone.Multiple stepwise regression analysis showed that BMI and HOMA-IR were independent risk factors of serum EDA.Conclusion Serum EDA is elevated in PCOS patients,especially when combined with obesity,which may be related to IR.Liraglutide intervention can significantly reduce EDA levels in PCOS patients.

Correlation between glycated hemoglobin index and insulin antibody positive in type 2 diabetes mellitus patients with poor oral hypoglycemic control / 中国糖尿病杂志

Objective To analyze the correlation between glycated hemoglobin index(HGI)and insulin antibody(IAA)positivity in type 2 diabetes mellitus(T2DM)patients with poorly controlled oral hypoglycemic agents.Methods A total of 260 T2DM patients with poor control of oral hypoglycemic agents and receiving insulin treatment in the Department of Endocrinology of Orthopedics and Diabetes Hospital of Haikou City from January 2020 to December 2021 were selected and divided into IAA positive group(n=75)and IAA negative group(n=185).Clinical data and biochemical indicators of the two groups were compared and analyzed the correlation between IAA positivity and other indicators.Results IAA positive group had a higher proportion of patients with insulin high dosage,insulin treatment time>2 years,and higher FIns,FPG,SUA and HGI than IAA negative group(P<0.05 or P<0.01),HbA1c≥9%lower than IAA negative group(P<0.01).Spearman correlation analysis showed that IAA positive was positively correlated with HGI(P<0.01),and negatively correlated with SUA and HDL-C(P<0.01).Logistic regression analysis showed that insulin treatment time,FIns,FPG,SUA,HbA1c and HGI were the influencing factors for IAA positive in T2DM patients.Receiver operating characteristic curve analysis showed that the area under the ROC curve for predicting IAA positive by HGI was 0.854,the optimal critical value for HGI was 0.4%,with the sensitivity 83.2%and the specificity 79.3%.Conclusion In T2DM patients with poorly controlled oral hypoglycemic drugs,high HGI has predictive value for IAA positivity.

Research progress in the metabolism of branched-chain amino acids and obesity related insulin resistance / 中国糖尿病杂志

Obese patients may have abnormal metabolism of branched-chain amino acids(BCAA).Elevated levels of BCAA can lead to insulin resistance(IR)through various mechanisms,which may make it a sensitive indicator for predicting the occurrence of diabetes mellitus.This article reviews the research progress on the correlation between BCAA metabolism,obesity and IR.

Research progress on dynamic modification and regulation of m6A methylation in insulin resistance / 中国糖尿病杂志

Insulin resistance(IR)is an abnormal pathological and physiological process characterized by a decrease in the ability of target tissues and organs to utilize insulin.There are many factors related to IR.Epigenetic modification is one of the important regulatory mechanisms that cause IR.N6-methyladenosine(m6A)is an epigenetic modification with high abundance in Eukaryote mRNA.Its dynamic changes can regulate the expression of related enzymes,affect IR process and exert different biological effects in target organs.This article reviews the research progress of dynamic modification and regulation of m6A methylation in IR.

Research progress in diabetic sarcopenia experiments / 中国糖尿病杂志

The occurrence of sarcopenia is closely related to diabetes mellitus(DM).The occurrence of sarcopenia in DM patients is often associated with insulin resistance,inflammation,myostatin and its complications.This article reviews the research progress of diabetic sarcopenia experiments.

Construction of small intestinal organoid model in insulin-resistant mice and protective effect of flavanomarein on intestinal mucosal barrier in this model / 中国药理学与毒理学杂志

OBJECTIVE To construct an insulin-resistant(IR)small intestinal organoid model of mice and study the protective effect of flavanomarein(FM)on the intestinal mucosal barrier in the model.METHODS ①Small intestinal organoid models of C57BL/6J and db/db of mice were constructed.The expressions of Ki-67,E-cadherin(E-cad),lysozyme(Lyz)and mucin-2(Muc-2)in small intestinal organ-oids were detected by 3D immunofluorescence.RT-qPCR was used to detect the expressions of fibro-nectin(Fn),glucagon-like peptide-1(GLP-1)and peotide YY(PYY)mRNA while Western blotting was used to detect the expressions of Fn,GLP-1 and PYY protein.The Lyz secretion level was detected by ELISA.② Small intestinal organoids were divided into five groups:C57BL/6J mice 'small intestinal organ-oids as the normal control group,db/db mice' intestinal organoids as the IR model group,db/db mice small intestinal organoids with flavanomarein 25,50 and 100 μmol·L-1 intervention for 48 h as IR model+ FM groups.RT-qPCR was used to detect the expression of Lyz mRNA while Western blotting was used to detect the expression of Lyz protein.RESULTS ① On the 6th day of small intestinal organoid culture,a ring structure with a clear luminal structure was formed and an IR mouse small intestinal organoid model was established.3D Immunofluorescence detection showed that the established small intestinal organoids all expressed Ki-67,E-cad,Lyz and MUC-2.Compared with the normal control group,the expres-sion of Fn mRNA in the IR model group was significantly increased(P<0.05)while the expressions of GLP-1 and PYY mRNA were significantly decreased(P<0.05).Compared with the normal control group,the expression of Fn protein in the IR model group was significantly decreased(P<0.05)while the expressions of GLP-1 and PYY protein were significantly increased(P<0.05).ELISA results showed that compared with the normal control group,the secretion levels of Lyz in the IR model group were signifi-cantly decreased(P<0.01).② RT-qPCR results showed that compared with the normal control group,the expression of Lyz mRNA in the IR model group was significantly decreased(P<0.01).Compared with the IR model group,the expression of Lyz mRNA in the IR model+FM 50 and 100 μmol·L-1 groups was significantly increased(P<0.05,P<0.01).Western blotting results showed that compared with the normal control group,the expression of Lyz protein in the IR model group was significantly decreased(P<0.01).Compared with the IR model group,the expression of Lyz protein in the IR model+FM 50 and 100 μmol·L-1 groups was significantly increased(P<0.05,P<0.01).CONCLUSION The constructed IR mouse small intestinal organoid model provides a more complete in vitro research model for exploring the pathophysiological mechanism by which drug interventions help repair the intestinal mucosal barrier.FM may maintain the intestinal mucosal barrier by reversing the decrease in Lyz expression levels in IR mice,thereby improving IR.

The increasement of blood METRNL protein by insulin sensitizer rosiglitazone / 药学实践与服务

Objective To investigate the effect of insulin sensitizer rosiglitazone on blood METRNL levels. Methods After fed with high fat diet (HFD) for 3 months, obese mice were treated with rosiglitazone for 1 month. Glucose tolerance was tested with glucose tolerance test (GTT), and METRNL levels in blood were measured by ELISA. Real time fluorescence quantitative PCR was used to detect the expression of METRNL in various tissues such as muscle, liver, white fat, brown fat, brain, spleen and kidney, as well as the expression of mitochondrial proteins in brown adipose tissue. Results Glucose tolerance of animals fed a high-fat diet was improved in rosiglitazone group, and blood METRNL levels were also increased significantly in this group. Rosiglitazone treatment increased the expression of METRNL in brown fat and kidney tissue. There was no effect on METRNL expression in muscle, liver, white fat, brain and spleen. Rosiglitazone increased the expression of mitochondrial-associated proteins in brown adipose tissue. Conclusion The insulin sensitizer rosiglitazone might increase the serum METRNL level by increasing the METRNL expression in brown fat and kidney tissue, suggesting that METRNL may be involved in the therapeutic effect of rosiglitazone on diabetes.

Analysis of Potential Active Ingredients and Mechanism of Baihu Jia Renshentang in Treatment of Obesity Complicated with Type 2 Diabetes Mellitus / 中国实验方剂学杂志

ObjectiveTo investigate the potential active ingredients and targets of Baihu Jia Renshentang（BHJRST） for the treatment of obesity combined with type 2 diabetes mellitus（T2DM） by network pharmacology and in vivo experiments. MethodUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to analyze and identify the material basis of BHJRST. Subsequently， potential targets for the action of the active ingredients were queried in databases such as ChEMBL， Therapeutic Target Database（TTD）， YaTCM， DisGeNET and Traditional Chinese Medicine on Immuno-Oncology（TCMIO）， and the shared targets were identified by taking the intersection of these targets with disease targets. The shared targets were imported into the STRING database to construct a protein-protein interaction（PPI） network， the hub genes were identified by cytoHubba plug-in， and molecular docking was used to validate the binding energy of the hub genes to the bioactive ingredients in BHJRST. Meanwhile， the shared targets were imported into the DAVID platform for gene ontology（GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis. The predicted results were subsequently verified by animal experiments. Eighteen 8-week-old male skeletal muscle insulin-like growth factor-1 receptor dysfunction（MKR） mice were induced by a high-fat diet for 12 weeks in order to prepare a mouse model of obesity combined with T2DM. The mice were randomly divided into the model group， metformin group（0.2 g·kg-1） and BHJRST group（27 g·kg-1 in raw material）， and another 6 male FVB mice of the same age as the normal group. The mice in each group were were given the corresponding drugs by gavage， and the normal and model groups were given the same amount of distilled water by gavage， 1 time/d for 6 consecutive weeks. At the end of administration， the body mass， Lee's index， fasting blood glucose（FBG）， oral glucose tolerance test（OGTT） of mice in each group were examined， and the pathological morphology of the white adipose tissue of the epididymis was observed， and the expression of the mRNA of the hub genes in the white adipose tissue of the epididymis was detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultA total of 200 bioactive components of BHJRST were identified， of which 64 bioactive components were reverse-matched to 384 targets， and a total of 308 targets were associated with obesity combined with T2DM. Hub genes included mitogen-activated protein kinase 1（MAPK1）， signal transducer and activator of transcription 3（STAT3）， MAPK3， interleukin（IL）-2， Janus kinase 1（JAK1）， nuclear transcription factor-κB p65（RELA）， estrogen receptor 1（ESR1）， transcription factor AP-1（JUN）， MAPK14 and lymphocyte-specific protein tyrosine kinase（LCK）. GO functional annotation showed that it was mainly enriched in cytoplasm， cell membrane and nucleus， and was closely related to important biological processes such as peptide serine phosphorylation， protein phosphorylation and inflammation. In KEGG enrichment analysis， metabolic pathway， lipid and atherosclerosis， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） and MAPK signal pathways were significantly enriched. The molecular docking results showed that the hub genes had a stable binding relationship with 10 bioactive components， including quercetin， isoliquiritigenin， and morin， in BHJRST. The results of animal experiments showed that BHJRST could significantly reduce body mass， Lee's index and FBG levels（P<0.01） in mice with obesity combined with T2DM， improve the pathological changes of white adipose tissue， and down-regulate the the mRNA expression of the hub genes in white adipose tissue of the epididymis（P<0.01）. ConclusionIn this study， 10 potentially active components such as quercetin， isoliquiritigenin， and morin in BHJRST are identified through network pharmacology and animal experiments， and it is possible to treat obesity combined with T2DM by regulating lipid and atherosclerosis， phosphatidylinositol PI3K/Akt and MAPK signal pathways， which provides important clues and theoretical basis for the study of its mechanism and clinical application.