Effect of Brassica rapa var. rapifera on Insulin Resistance and Inflammatory Analysis of Visceral Adipose Tissue of Obese Wistar Rats Under Glucolipotoxicity Condition / Efecto de Brassica rapa var. rapifera sobre la Resistencia a la Insulina y el Análisis Inflamatorio del Tejido Adiposo Visceral de Ratas Wistar Obesas en Condiciones de Glucolipotoxicidad

SUMMARY: Obesity-related pathophysiologies such as insulin resistance and the metabolic syndrome show a markedly increased risk for type 2 diabetes and atherosclerotic cardiovascular disease. This risk appears to be linked to alterations in adipose tissue function, leading to chronic inflammation and the dysregulation of adipocyte-derived factors. Brassica rapa have been used in traditional medicine for the treatment of several diseases, including diabetes. This study aimed to investigate the effect of nutritional stress induced by a high-fat and high-sucrose diet on the pathophysiology of visceral adipose tissue and the therapeutic effect of Brassica rapa in male Wistar rats. We subjected experimental rats to a high-fat (10 %) high-sucrose (20 %)/per day for 11 months and treated them for 20 days with aqueous extract Br (AEBr) at 200 mg/kg at the end of the experiment. At the time of sacrifice, we monitored plasma and tissue biochemical parameters as well as the morpho-histopathology of visceral adipose tissue. We found AEBr corrected metabolic parameters and inflammatory markers in homogenized visceral adipose tissue and reduced hypertrophy, hyperplasia, and lipid droplets. These results suggest that AEBr enhances anti-diabetic, anti-inflammatory and a protective effect on adipose tissue morphology in type 2 diabetes and obesity.

La fisiopatología relacionadas con la obesidad, como la resistencia a la insulina y el síndrome metabólico, muestran un riesgo notablemente mayor de diabetes tipo 2 y enfermedad cardiovascular aterosclerótica. Este riesgo parece estar relacionado con alteraciones en la función del tejido adiposo, lo que lleva a una inflamación crónica y a la desregulación de los factores derivados de los adipocitos. Brassica rapa se ha utilizado en la medicina tradicional para el tratamiento de varias enfermedades, incluida la diabetes. Este estudio tuvo como objetivo investigar el efecto del estrés nutricional inducido por una dieta rica en grasas y sacarosa sobre la fisiopatología del tejido adiposo visceral y el efecto terapéutico de Brassica rapa en ratas Wistar macho. Sometimos a ratas experimentales a una dieta rica en grasas (10 %) y alta en sacarosa (20 %)/por día durante 11 meses y las tratamos durante 20 días con extracto acuoso de Br (AEBr) a 200 mg/kg al final del experimento. En el momento del sacrificio, monitoreamos los parámetros bioquímicos plasmáticos y tisulares, así como la morfohistopatología del tejido adiposo visceral. Encontramos parámetros metabólicos corregidos por AEBr y marcadores inflamatorios en tejido adiposo visceral homogeneizado y reducción de hipertrofia, hiperplasia y gotitas de lípidos. Estos resultados sugieren que AEBr mejora el efecto antidiabético, antiinflamatorio y protector sobre la morfología del tejido adiposo en la diabetes tipo 2 y la obesidad.

Relationship between vitamin B12 levels and insulin resistance in postmenopausal women from Colombia Caribbean / Relação entre níveis de vitamina B12 e resistência à insulina em mulheres na pós-menopausa da Colômbia Caribe

Introduction: The high prevalence of low vitamin B12 serum levels has been recognized as a public health problem in Latin America; however, the current magnitude of this deficiency in Colombia is uncertain. Low levels of vitamin B12 can induce clinical and subclinical hematological and neurological disorders. Epidemiological studies have demonstrated a relationship between vitamin B12 deficiency and cardiovascular diseases (CVDs). However, the role of vitamin B12 in insulin resistance has been poorly studied. Objective: This study aimed to evaluate the relationship between vitamin B12 serum levels and biochemical and anthropometric markers related to CVDs and insulin resistance in postmenopausal women from Colombia Caribbean. Methods: Correlational, descriptive study. By convenience sampling, 182 postmenopausal women from the medical consultation service of a health institution were linked. Serum vitamin B12 levels, anthropometric variables (body mass index, abdominal perimeter), and biochemical variables (glycemia, insulin, lipid profile, HOMA IR) were evaluated. Results: The average value of the vitamin B12 serum level was 312.5 ± 122.5 pg/mL (230.6 ± 90.4 pmol/L); 46.7% of the women had less than adequate levels of 300 pg/mL (> 221 pmol/L), and 9. 9% were deficient, with levels of less than 200 pg/mL (148 pmol/L). The women with metabolic syndrome were 63.7%, and according to HOMA IR, 52.7 % had insulin resistance. A significant inverse relationship was shown between serum vitamin B12 levels with basal glycemic (P =0.002) and HOMA-IR (P =0.040). Conclusions: A significant inverse relationship between vitamin B12 levels and basal glycemia and HOMA-IR was observed. These findings highlight vitamin B12 deficiency in postmenopausal women and suggest nutritional supplementation.Keywords: Vitamin B12, Insulin resistance, Diet, Postmenopause, Cardiovascular diseases (AU).

Introdução: A alta prevalência de baixos níveis séricos de vitamina B12 foi reconhecida como um problema de saúde pública na América Latina, mas a magnitude atual dessa deficiência na Colômbia é incerta. Baixos níveis de vitamina B12 podem induzir distúrbios hematológicos e neurológicos clínicos e subclínicos. Na verdade, estudos epidemiológicos demonstram uma relação entre deficiência de vitamina B12 e doenças cardiovasculares (DCVs). No entanto, o papel da vitamina B12 na resistência à insulina tem sido pouco estudado. Objetivo: O objetivo deste estudo foi avaliar a relação entre os níveis séricos de vitamina B12 e marcadores bioquímicos e antropométricos relacionados com doenças cardiovasculares e resistência à insulina em mulheres pós-menopáusicas da Colômbia Caribe. Métodos: Estudo correlacional, descritivo. Por amostragem de conveniência, foram vinculadas 182 mulheres na pós-menopausa do serviço de consulta médica de uma instituição de saúde. Níveis séricos de vitamina B12, variáveis antropométricas (índice de massa corporal, perímetro abdominal) e variáveis bioquímicas (glicemia, insulina, perfil lipídico, HOMA IR) foram avaliadas. Resultados: O valor médio do nível sérico de vitamina B12 foi de 312,5 ± 122,5 pg/mL (230,6 ± 90,4 pmol/L); 46,7% das mulheres tinham níveis abaixo do adequado de 300 pg/mL (> 221 pmol/L), e 9,9% eram deficientes, com níveis abaixo de 200 pg/mL (148 pmol/L).As mulheres com síndrome metabólica foram 63,7% e, segundo o HOMA IR, 52,7% apresentavam resistência à insulina. Uma relação inversa significativa entre os níveis séricos de vitamina B12 com glicemia basal (P = 0,002) e HOMA-IR (P = 0,040) foi mostrada. Conclusões: Foi observada uma relação inversa significativa entre os níveis de vitamina B12 e glicemia basal e HOMA-IR. Esses achados destacam a deficiência de vitamina B12 em mulheres na pós-menopausa e sugerem suplementação nutricional (AU).

Síndrome metabólico en el adulto mayor vinculado a los programas de actividad física comunitaria / Metabolic Syndrome in the Elderly Adult Involved in the Community Physical Activity Programs

Introducción: El síndrome metabólico es una situación clínica compleja que se asocia a un incremento de la morbilidad y mortalidad. Los elementos que lo componen aumentan el riesgo de diabetes mellitus tipo II y enfermedad cardiovascular. Objetivo: Determinar el comportamiento del síndrome metabólico en el adulto mayor vinculado a los programas de actividad física comunitaria del proyecto Lindo Amanecer del municipio Arroyo Naranjo. Métodos: Se realizó un estudio observacional descriptivo de corte transversal. El universo de estudio lo constituyeron 120 adultos mayores, de los que se entrevistaron a 106, en el período de abril a octubre de 2018. Se siguieron los criterios del Adult Treatment Panel III para el diagnóstico de síndrome metabólico. Las variables descriptivas se expresaron en porcientos y para la comparación de variables en estudio se utilizó el método estadístico de ji al cuadrado. Resultados: Los resultados obtenidos mostraron un 41,51 por ciento de personas con síndrome metabólico, predominaron las personas de 70 y más años de edad (54,54 por ciento y el sexo femenino (93,18 por ciento). El 100 por ciento tuvieron cifras de presión arterial ≥ 130/85 mmHg. El 100 por ciento de los pacientes desconocían su enfermedad. Conclusiones: Se encontró predominio en los pacientes con síndrome metabólico del sexo femenino y del grupo de edad de 70 y más años. El diagnóstico a nivel de la Atención Primaria de Salud es deficiente. Se asocia a la hipertensión arterial, obesidad abdominal y al riesgo de enfermedad cardiovascular(AU)

Introduction: Metabolic syndrome is a complex clinical situation associated with an increase in morbidity and mortality. The elements that mark it up increase the risk of type 2 diabetes mellitus and cardiovascular disease. Objective: To determine the behavior of metabolic syndrome in elderly adults involved in the community physical activity programs of the Lindo Amanecer project in the municipality of Arroyo Naranjo. Methods: A cross-sectional descriptive observational study was carried out. The study universe was made up of 120 elderly adults, 106 of which were interviewed in the period from April to October 2018. The Adult Treatment Panel III criteria for the diagnosis of metabolic syndrome were followed. The descriptive variables were expressed in percentages and, for the comparison of variables under study, the chi-square statistical method was used. Results: The obtained results showed 41.51percent of people with metabolic syndrome, with a predominance of people aged 70 years and older (54.54percent) and the female sex (93.18percent). One hundred percent had blood pressure values over or equal to 130/85 mmHg. One hundred percent of the patients did not have any knowledge of their disease. Conclusions: In patients with metabolic syndrome, the predominance corresponded to the female sex, as well as the age group of 70 years and older. Diagnosis at the primary healthcare level is deficient. It is associated with arterial hypertension, abdominal obesity and the risk of cardiovascular disease(AU)

Influencia de la seropositividad contra adenovirus-36 sobre riesgo de obesidad y resistencia a la insulina en población infanto-juvenil de la Región de la Araucanía / Influence of adenovirus 36 seropositivity on the risk of obesity and insulin resistance in a population of children and adolescents from the Región de la Araucanía

La infección previa por el adenovirus-36 (Ad-36) se ha asociado con el proceso adipogénico y el control glicémico en modelos experimentales de cultivos celulares y animales. En humanos, la presencia de anticuerpos contra Ad-36 ha mostrado aumentar el riesgo de obesidad y, paradójicamente, mejorar el control glicémico en diferentes poblaciones. Se evaluó la influencia de la seropositividad contra Ad-36 sobre riesgo de obesidad, el perfil lipídico y glicémico en una población de niños en edad escolar. Métodos: Doscientos ocho individuos de entre 9 y 13 años se agruparon según estado nutricional como normopeso (IMC z-score de -1 a +1), con sobrepeso (IMC z-score de +1 a +2) y con obesidad (IMC z-score > +3). Se evaluaron medidas antropométricas, desarrollo puberal según Tanner y parámetros bioquímicos (perfil lipídico, glucemia e insulina) y la seropositividad contra Ad-36. Se determinó la resistencia a la insulina (RI) según criterio para la población infantil chilena. La seropositividad contra Ad-36 se determinó mediante ELISA. Resultados: Hubo una alta prevalencia de sobrepeso/obesidad en la población de estudio. La seropositividad contra Ad-36 fue del 5,4% en el grupo total, pero no se observó una asociación con el estado nutricional. No se encontró correlación entre la seropositividad contra Ad-36 y los parámetros del perfil lipídico. La insulina y la HOMA-RI fueron significativamente más bajas en el grupo Ad-36 (+) (p<0,001), no habiendo sido reportados casos de RI en el grupo Ad-36 (+) en nuestra población. Conclusiones: Nuestros resultados sugieren que la infección previa por el adenovirus-36 afecta la secreción de insulina y la resistencia a la insulina, como se ha descrito anteriormente, sin embargo, no se observa correlación con el desarrollo de la obesidad infantil en la población pediátrica del sur de Chile.

Previous infection with Adenovirus-36 (Ad-36) has been associated with adipogenic process and glycemic control in experimental models of cell culture and animals. In humans, the presence of antibodies against Ad-36 has been shown to increase the risk of obesity and, paradoxically, improve glycemic control in different populations. The influence of Ad-36 seropositivity on obesity risk, lipid and glycemic profile was evaluated in a population of school-age children. Methods: Two hundred eight individuals aged 9 to 13 years were grouped according to their nutritional status as normal weight (BMI z-score from -1 to +1), overweight (BMI z-score from +1 to +2) or obese (BMI z-score from -1 to +1). z-score > +3). Anthropometric measurements, pubertal development according to Tanner stage, biochemical parameters (lipid profile, glycemia and insulin) and seropositivity against Ad-36 were evaluated. Insulin resistance (IR) was determined according to criteria for the Chilean child population. Seropositivity against Ad-36 was determined by ELISA. Results: There was a high prevalence of overweight/obesity in the study population. Seropositivity against Ad-36 was 5.4% in the total group, but no association with nutritional status was observed. No correlation was found between Ad-36 seropositivity and lipid profile parameters. Insulin and HOMA-RI were significantly lower in the Ad-36 (+) group (p<0.001), and no cases of RI were reported in the Ad-36 (+) group in our population. Conclusions: Our results suggest that previous adenovirus-36 infection affects insulin secretion and insulin resistance, as previously described, however, no correlation is observed with the development of childhood obesity in the pediatric population. from southern Chile.

El Estimador de Sensibilidad Insulínica de Punto Único (SPISE) supera a marcadores antropométricos de uso rutinario en la pesquisa de riesgo cardiometabólico asociado a obesidad: un estudio en adolescentes de la Región Metropolitana / The single Point Insulin Sensitivity Estimator (SPISE) outperforms routine anthropometric markers in the screening of obesity-related cardiometabolic risk: a study in adolescents from the Metropolitan Region

El Estimador de Sensibilidad a la Insulina de Punto Único (SPISE) es un biomarcador de sensibilidad a la insulina comparable al Índice de Matsuda. Se estima utilizando el IMC y los niveles de triglicéridos y HDL. El objetivo de este estudio fue comparar el rendimiento diagnóstico de SPISE con el de otros marcadores antropométricos de uso rutinario, como el IMC y la relación cintura | talla, en la pesquisa de insulinoresistencia (IR) y Síndrome Metabólico (MetS) en una muestra de 901 adolescentes de 11 a 16 años. En todos ellos se midió peso, talla, cintura, presión arterial, perfil lipídico, insulina y glicemia. La IR se diagnosticó con el HOMA-IR y el MetS con el criterio de Cook. Un zIMC ≥2.0 DE, un índice cintura/ talla ≥0.54 y un SPISE ≤ 5.4 fueron los puntos de corte utilizados para evaluar el rendimiento de estos marcadores en el diagnóstico de IR y MetS. No hubo diferencias por sexo en la prevalencia de obesidad, IR y MetS. Tanto en hombre como en mujeres, SPISE mostro una mejor capacidad para predecir el MetS (AUC: 0.95 y 0.89, respectivamente) e IR (AUC: 0.83 y 0.79, respectivamente) comparado con el rendimiento diagnóstico de la relación cintura | talla y el IMC-z. De igual manera, el SPISE mostro una mayor sensibilidad para identificar a los portadores de MetS e IR (96% y 75% en varones y 81% y 67% en mujeres, respectivamente). SPISE mostró una mejor capacidad para identificar el riesgo cardiometabólico asociado a la malnutrición por exceso al compararlo con otros indicadores de uso frecuente en clínica. Un índice de SPISE ≤5.4 fue un mejor predictor de MetS e IR que un IMC ≥2.0 DE y una relación cintura | talla ≥0.54.

The Single Point Insulin Sensitivity Estimator (SPISE) is a biomarker of insulin sensitivity comparable to the Matsuda Index. It is estimated using data on BMI, TG, and HDL. We aim to compare the diagnostic performance of SPISE with other routinely used anthropometric markers, such as BMI and waist-to-height ratio, in diagnosing insulin resistance (IR) and Metabolic Syndrome (MetS) in adolescents from 11 to 16 years. Weight, height, waist, blood pressure, lipid profile, insulin, and glycemia were measured. IR was diagnosed with the HOMA-IR and the MetS with the Cook criteria. A BMIz ≥2.0 SD, a waist-to-height ratio ≥0.54, and a SPISE ≤ 5.4 were the cut-off points used for diagnosing IR and MetS. There were no sex differences in the prevalence of obesity, IR, and MetS. In both males and females, SPISE showed a better ability to predict MetS (AUC: 0.95 and 0.89, respectively) and IR (AUC: 0.83 and 0.79, respectively) compared to the waist-to-height ratio and BMI-z. Similarly, SPISE showed greater sensitivity to identify adolescents with MetS and IR (96% and 75% in men and 81% and 67% in women, respectively) than the waist-to-height ratio and BMI-z. SPISE performed better in identifying obesity-related cardiometabolic risk than other frequently used clinical indicators. A SPISE index ≤5.4 was a better predictor of MetS and RI than a BMI ≥2.0 SD and a waist-to-height ratio ≥0.54.

Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation / 医学前沿

Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual's health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique "continuous glucose monitoring" (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend < 0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P < 0.01), and multiple linear stepwise regression showed that the disposition index, which reflects β-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P < 0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

Associations Between Insulin Resistance Indexes and Hyperuricemia in Hypertensive Population / 中国医学科学院学报

Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.

Predictive Effects of Different Insulin Resistance Indexes on Diabetes Risk in Hypertensive Population / 中国医学科学院学报

Objective To explore the roles of different insulin resistance indexes[triglyceride-glucose (TyG),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and metabolic score for insulin resistance (METS-IR)]and combinations of two indexes in predicting diabetes risk in hypertensive population. Methods The survey of hypertension was conducted for the residents in Wuyuan county,Jiangxi province from March to August in 2018.The basic information of hypertensive residents was collected by interview.Blood was drawn on an empty stomach in the morning and physical measurements were carried out.Logistic regression model was employed to analyze the relationship between different insulin resistance indexes and diabetes,and the area under the receiver operating characteristic curve was used for evaluating the predictive effects of each index on diabetes risk. Results A total of 14 222 hypertensive patients with an average age of (63.8±9.4) years old were included in this study,including 2616 diabetic patients.The diabetic hypertensive population had higher TyG (t=50.323,P<0.001),TG/HDL-C (Z=17.325,P<0.001),and METS-IR (t=28.839,P<0.001) than the non-diabetic hypertensive population.Multivariate analysis showed that each insulin resistance index was positively correlated with diabetes risk.The area under curve of each insulin index was in a descending order of TyG (0.770)> METS-IR (0.673)> TG/HDL-C (0.620).The difference in the area under curve between two indexes was statistically significant[TyG vs.TG/HDL-C (Z=42.325,P<0.001);TyG vs.METS-IR(Z=17.517,P<0.001);METS-IR vs.TG/HDL-C (Z=10.502,P<0.001)]. Conclusions Elevated insulin resistance indexes can increase the risk of diabetes.TyG and the combination of indexes outperform TG/HDL-C and METS-IR in the prediction of diabetes.

Regulatory effects and mechanisms of branched chain amino acids and metabolic intermediates on insulin resistance / 生理学报

Branched chain amino acids, as essential amino acids, can be used to synthesize nitrogen-containing compounds and also act as signal molecules to regulate substance metabolism. Studies have shown that the elevated level of branched chain amino acids is closely related to insulin resistance and type 2 diabetes. It can affect insulin signal transduction by activating mammalian target of rapamycin (mTOR) signal pathway, and regulate insulin resistance by damaging lipid metabolism and affecting mitochondrial function. In addition, abnormal catabolism of branched amino acids can lead to the accumulation of metabolic intermediates, such as branched chain α-keto acids, 3-hydroxyisobutyrate and β-aminoisobutyric acid. Branched chain α-keto acids and 3-hydroxyisobutyrate can induce insulin resistance by affecting insulin signaling pathway and damaging lipid metabolism. β-aminoisobutyric acid can improve insulin resistance by reducing lipid accumulation and inflammatory reaction and enhancing fatty acid oxidation. This paper systematically reviewed the regulatory effects and mechanisms of branched chain amino acids and their metabolic intermediates on insulin resistance, which will provide a new direction for the prevention and treatment of insulin resistance and type 2 diabetes.

Glycogen synthase kinase-3 (GSK-3) a magic enzyme: it's role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review / Glicogênio sintase quinase-3 (GSK-3), uma enzima mágica: seu papel no diabetes mellitus e na homeostase da glicose: interações com fluoroquinolonas. Uma mini-revisão

Abstract Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer's disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

Resumo O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis ​​pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

The relationship between admission insulin resistance index (AIRI) and in-hospital outcome in non-diabetic acute coronary syndrome / Journal of the ASEAN Federation of Endocrine Societies

Background@#Acute coronary syndrome (ACS) is a major cardiovascular problem due to its high hospitalization and mortality rates. One of the risk factors for atherosclerosis that leads to ACS is insulin resistance (IR) which plays a role in the pathogenesis and development of cardiovascular events. This study aims to determine the relationship between IR and in-hospital outcomes in non-diabetic patients with ACS.@*Methodology@#This was a cohort study conducted from January-June 2021. Insulin resistance was assessed using the Admission insulin resistance index (AIRI). This measurement was performed once during the patient's admission, and then the outcome was observed during hospitalization. The observed in-hospital outcomes were composite outcomes; namely, heart failure, arrhythmia, cardiogenic shock, and death. The statistical tests used were ANOVA, independent T and Chi-Square tests. Statistical test results were considered significant if p<0.05.@*Results@#This study included 60 subjects (51 males and 9 females). Analysis revealed that AIRI was higher in patients with composite outcomes (mean 9.97 ± 4.08) than in patients without composite outcomes (mean 7.71 ± 4.06) (p<0.05); AIRI was higher in patients with heart failure (mean 10.72 ± 3.83) than in patients without heart failure (mean 7.25 ± 3.84) (p<0.001). Patients with IR had a higher rate of heart failure complications [OR 5.5 95% CI (1.56-19.38) (p=0.005)].@*Conclusion@#There is an association between AIRI and composite outcomes. Patients with IR have 5.5 times the risk of developing heart failure.

Effect of yoga and walking on glycemic control for the management of type 2 diabetes: A systematic review and meta-analysis / Journal of the ASEAN Federation of Endocrine Societies

Background@#A daily habit of yogic practice or walking, along with an oral hypoglycemic agent (OHA) could be beneficial for better control of type 2 diabetes mellitus (T2DM). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to find out the efficiency of yoga or walking on glycemic control in T2DM.@*Methodology@#The present systematic review and meta-analysis were completed according to the PRISMA guidelines. The risk of bias in included studies was evaluated, by using the revised Cochrane risk-of-bias tool for randomized trials. Meta-analysis was implemented using RevMan software. Forest plots were used to illustrate the study findings and meta-analysis results.@*Results@#Sixteen studies were included in this systematic review, where 1820 participants were allocated to one of the following interventions: yoga, walking, and without any regular exercise (control group). Participants were between 17–75 years of age. Compared to the control group, the yoga group had a significant reduction in fasting blood glucose (FBG) by 31.98 mg/dL (95% CI,–47.93 to –16.03), postprandial blood glucose (PPBG) by 25.59 mg/dL (95% CI, –44.00 to –7.18], glycosylated hemoglobin (HbAlc) by 0.73% (95% CI, –1.24 to -0.22), fasting insulin by 7.19 μIU/mL (95% CI, –12.10 to –2.28), and homeostatic model assessment for insulin resistance (HOMA-IR) by 3.87 (95% CI, –8.40 to -0.66). Compared to the control group, the walking group had a significant reduction in FBG by 12.37 mg/dL (95% CI, –20.06 to –4.68) and HbA1c by 0.35% (95% CI, –0.70 to –0.01). Compared to the walking group, the yoga group had a significant reduction in FBG by 12.07 mg/dL (95% CI, –24.34 to – 0.20), HbA1c by 0.20% (95% CI, –0.37 to –0.04), fasting insulin by 10.06 μIU/mL (95% CI, –23.84 to 3.71) and HOMA-IR by 5.97 (95% CI, –16.92 to 4.99).@*Conclusions@#Yoga or walking with OHA has positive effects on glycemic control. For the management of T2DM, yoga has relatively more significant effects on glycemic control than walking.

The role of adipose-derived exosomes in the pathological progression of atherosclerosis / 生理学报

Atherosclerosis is a chronic inflammatory disease of vascular walls with a complex etiology. In recent years, the incidence of atherosclerosis continues to increase with obesity and diabetes as major risk factors. As an important metabolic organ in the body, adipose tissue also has a powerful endocrine function. In the case of obesity and diabetes, various cytokines and exosomes derived from adipose tissue mediate organ-organ/cell-cell crosstalk, and are involved in the occurrence and development of various diseases. As an important intercellular communicator, exosomes regulate the pathological process of various cardiovascular diseases and are closely related to atherosclerosis. In this paper, we reviewed the mechanism of adipose-derived exosomes in atherosclerosis with focus on endothelial dysfunction, inflammatory response, lipid metabolism disorder and insulin resistance, hoping to provide reference for the research, diagnosis and treatment of atherosclerosis.

Nuclear factor-Y mediates pancreatic β-cell compensation by repressing reactive oxygen species-induced apoptosis under metabolic stress / 中华医学杂志(英文版)

BACKGROUND@#Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear.@*METHODS@#In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress.@*RESULTS@#Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment.@*CONCLUSION@#Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.

Effect of electroacupuncture on liver Akt/FoxO1 signaling pathway in rats with diabetic fatty / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on liver protein kinase B (Akt)/forkhead box transcription factor 1 (FoxO1) signaling pathway in Zucker diabetic fatty (ZDF) rats, and to explore the possible mechanism of EA on improving liver insulin resistance of type 2 diabetes mellitus.@*METHODS@#Twelve male 2-month-old ZDF rats were fed with high-fat diet for 4 weeks to establish diabetes model. After modeling, the rats were randomly divided into a model group and an EA group, with 6 rats in each group. In addition, six male Zucker lean (ZL) rats were used as the blank group. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20). The ipsilateral "Zusanli" (ST 36) and "Weiwanxiashu" (EX-B 3) were connected to EA device, continuous wave, frequency of 15 Hz, 20 min each time, once a day, six times a week, for a total of 4 weeks. The fasting blood glucose (FBG) in each group was compared before modeling, before intervention and after intervention; the serum levels of insulin (INS) and C-peptide were measured by radioimmunoassay method, and the insulin resistance index (HOMA-IR) was calculated; HE staining method was used to observe the liver tissue morphology; Western blot method was used to detect the protein expression of Akt, FoxO1 and phosphoenolpyruvate carboxykinase (PEPCK) in the liver.@*RESULTS@#Before intervention, compared with the blank group, FBG was increased in the model group and the EA group (P<0.01); after intervention, compared with the model group, FBG in the EA group was decreased (P<0.01). Compared with the blank group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were increased (P<0.01), while the protein expression of hepatic Akt was decreased (P<0.01) in the model group. Compared with the model group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were decreased (P<0.01), while the protein expression of hepatic Akt was increased (P<0.01) in the EA group. In the model group, the hepatocytes were structurally disordered and randomly arranged, with a large number of lipid vacuoles in the cytoplasm. In the EA group, the morphology of hepatocytes tended to be normal and lipid vacuoles were decreased.@*CONCLUSION@#EA could reduce FBG and HOMA-IR in ZDF rats, improve liver insulin resistance, which may be related to regulating Akt/FoxO1 signaling pathway.

Alkaloids from fruit of Lycium chinense var. potaninii / 中国中药杂志

Ten alkaloids(1-10) were isolated from the ethyl acetate extract of the fruit of Lycium chinense var. potaninii by silica gel, ODS, and preparative high performance liquid chromatography(HPLC), and identified by NMR and MS as methyl(2S)-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(1), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(phenyl)propanoate(2), 3-hydroxy-4-ethyl ketone pyridine(3), indolyl-3-carbaldehyde(4),(R)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde(5),(R)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-car-baldehyde(6), methyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]-3-(4-hydroxyphenyl)propanoate(7), dimethyl(2R)-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanedioate(8), 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoate(9), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid(10). All the compounds were isolated from the plant for the first time. Among them, compounds 1-3 were new compounds. Compounds 1-9 were evaluated for hypoglycemic activity in vitro with the palmitic acid-induced insulin resistance in HepG2 cells. At 10 μmol·L~(-1), compounds 4, 6, 7, and 9 can promote the glucose consumption of HepG2 cells with insulin resistance.

Research progress on chemical constituents of Schisandra chinensis and its effect on nonalcoholic fatty liver disease / 中国中药杂志

Schisandra chinensis, a traditional Chinese medicinal herb, is rich in chemical constituents, including lignans, triterpenes, polysaccharides, and volatile oils. Clinically, it is commonly used to treat cardiovascular, cerebrovascular, liver, gastrointestinal, and respiratory diseases. Modern pharmacological studies have shown that S. chinensis extract and monomers have multiple pharmacological activities in lowering liver fat, alleviating insulin resistance, and resisting oxidative stress, and have good application prospects in alleviating nonalcoholic fatty liver disease(NAFLD). Therefore, this study reviewed the research progress on chemical constituents of S. chinensis and its effect on NAFLD in recent years to provide references for the research on S. chinensis in the treatment of NAFLD.

Anti-obesity and Gut Microbiota Modulation Effect of Astragalus Polysaccharides Combined with Berberine on High-Fat Diet-Fed Obese Mice / 中国结合医学杂志

OBJECTIVE@#To investigate whether astragalus polysaccharides (APS) combined with berberine (BBR) can reduce high-fat diet (HFD)-induced obesity in mice.@*METHODS@#Except for normal mice, 32 HFD-induced obese mice were randomized into HFD, APS (1,000 mg/kg APS), BBR (200 mg/kg BBR), and APS plus BBR (1,000 mg/kg APS plus 200 mg/kg BBR) groups, respectively. After 6-week treatment (once daily by gavage), the obesity phenotype and pharmacodynamic effects were evaluated by histopathological examination of epididymal fat, liver, and colon using hematoxylin-eosin staining and serum biochemical analyses by an automated chemistry analyzer. The feces were collected at the 12 th week, and taxonomic and functional profiles of gut microbiota were analyzed by 16S ribosomal ribonucleic acid (16S rRNA) sequencing.@*RESULTS@#Compared with HFD group, the average body weight of APS plus BBR group was decreased (P<0.01), accompanied with the reduced fat accumulation, enhanced colonic integrity, insulin sensitivity and glucose homeostasis (P<0.05 or P<0.01). Importantly, APS combined with BBR treatment was more effective than APS or BBR alone in improving HFD-induced insulin resistance (P<0.05 or P<0.01). 16S rRNA sequence-based analysis of fecal samples demonstrated that APS combined with BBR treatment exhibited a better impact on HFD-induced gut microbiota dysbiosis, exclusively via the enriched abundances of Bacteroides, which corresponded to the large increase of predicted bacterial genes involved in carbohydrate metabolism.@*CONCLUSION@#APS combined with BBR may synergistically reduce obesity and modulate the gut microbiota in HFD-fed mice.

Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway / 中国中药杂志

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.