Persistent hyperglycemia induced by chronic restraint stress in rat is associated with nucleus tractus solitarius injury / 解剖学报

Objective: To investigate the role of anterior part of commissural subnucleus of nucleus tractus solitarius (acNTS) injury in insulin-resistant hyperglycemia during chronic restraint stress (CRS). Methods: We produced the CRS models (n = 20, a 7-day restraint followed by a 3-day free moving procedure for 40 days) in rats, and detected the parameters related to glucose metabolism. Results: The CRS induced a moderate (not higher than 11 mmol/L) and irreversible insulin-resistant hyperglycemia in about 1/3 (n = 7) of the individuals. CRS-hyperglycemic rats showed a condensed staining of acNTS neurons, and Caspase-3 immunostaining and TUNEL also showed positive, indicating apoptotic changes of acNTS neurons. After acNTS mechanical damage (n= 6), the blood glucose level rised gradually, which also led to insulin-resistant hyperglycemia. The characteristics of hyperinsulinemia, increased islet volume, and serum corticosterone levels in acNTS mice were consistent with those of CRS mice. Conclusion: The result indicates that during CRS, injury (apoptosis) of glucose-sensitive acNTS neurons causes dysregulation of blood glucose. Restraint stress model has value as a potential application in the study of stress-induced hyperglycemia.

Zinc, cobre y vitaminas C, E y A en púberes con exceso de peso y resistencia a la insulina / Zinc, copper and vitamins C, E and A in a pubertal overweight and insulin-resistant population / Zinco, cobre e vitaminas C, E e A em púberes com excesso de peso e resistência à insulina

Las vitaminas (Vit.) C, E y A, junto al zinc (Zn++) y cobre (Cu++) colaboran en la prevención de las comorbilidades asociadas a la obesidad. El objetivo del trabajo fue evaluar las concentraciones séricas (Cs) de Vit. C, E y A, así como las del Zn++ y Cu++ en púberes con exceso de peso (EP) y resistencia a la insulina (RI). El estudio fue descriptivo, correlacional, de campo y transversal. Las variables se compararon entre los púberes normopeso (NP)/sin RI y quienes tenían EP (con y sin RI). Se emplearon las pruebas de Pearson y Spearman, test de Student, U de Mann-Whitney, Kruskal-Wallis y el estadístico Z. Los adolescentes con EP/RI presentaron Cs de Zn++ menores que aquellos con EP/sin RI, y que el grupo control (p=0,010), siendo probablemente la RI lo que define esta disminución ya que el Zn++ fue similar entre los púberes con y sin EP. El 12,0% de los sujetos con EP/RI presentaron la relación Vit. E/Colesterol Total (CT)< 2,25 mmol/mol, comparados con el 4,8% y 8,0% observado en los adolescentes con EP/sin RI y los controles, respectivamente (p=0,012). Los adolescentes con EP/ RI evidenciaron una menor protección antioxidante y Cs de Zn++ inferiores al resto de los grupos evaluados.

Vitamins (Vit.) C, E and A, together with zinc (Zn++) and copper (Cu++) play an important role in the prevention of comorbidities associated with obesity. The objective of this work was to evaluate serum concentrations (Sc) of Vit. C, E and A, and those of Zn++ and Cu++ in a pubertal overweight (OW) and insulin-resistant (IR) population. The study was descriptive, correlational and cross-sectional. Variables were compared between the normalweight pubescent population, non-IR and those OW (IR or non-IR). Correlations between variables were assessed using Pearson and Spearman tests, the Student t test, Mann-Whitney U test, Kruskal-Wallis test and the statistical Z. OW and IR adolescents presented lower Zn++ than those OW non-IR, and the control group (p=0.010). Probably it is being IR what defines this decrease since the Zn++ was similar in the pubertal population with and without OW. In the OW and RI group of adolescents, there was a frequency of alterations in vit. E/CT (<2.25 mmol/mol) of 12.0%, compared to 4.8% and 8.0% in OW and non-IR and control adolescents, respectively (p=0.012) OW and IR adolescents showed a lower antioxidant protection and lower Zn++ than other groups evaluated.

As vitaminas (Vit.) C, E e A, em conjunto com zinco (Zn++) e Cobre (Cu++) desempenham um papel importante na prevenção de comorbidades associadas à obesidade. O objetivo do trabalho foi avaliar as concentrações séricas (Cs) de Vit. C, E e A, bem como as de Zn++ e de Cu++ em púberes com excesso de peso (EP) e resistência à insulina (RI). O estudo foi descritivo, correlacional, de campo e transversal. As variáveis foram comparadas entre os púberes normopeso (NP)/sem RI e aqueles que tinham EP (com e sem RI). Foram utilizados os testes de Pearson e Spearman, teste de Student, U de Mann- Whitney, Kruskal-Wallis e o estatístico Z. Adolescentes com EP/RI apresentaram Cs de Zn++ menores do que aqueles com EP/sem RI, e que o grupo controle (p=0,010), sendo provavelmente a RI o que define esta diminuição, visto que o Zn++ foi similar entre os púberes com e sem EP. 12,0% de sujeitos com EP/RI apresentaram a relação Vit. E/Colesterol Total (CT) <2,25 mmol/mol, comparados com 4,8% e 8,0% observado nos adolescentes com EP/sem RI e os controles, respectivamente (p=0,012). Adolescentes com EP e RI mostraram menor proteção antioxidante e Cs de Zn++ inferiores ao resto dos grupos avaliados.

Polimorfismo PRO12ALA del gen PPARy2, ALA54THR del gen FABP2 y polimorfismos del gen de alipoproteina E en habitantes del sector los eucaliptos de la parroquia san juan, munisipio libertador / PRO12ALA polymorhism of the PPARy2 gene, ALA54THR polymorphism of the FABP2 gene and polymorphisms of the apolipoprotein E gene in the population of Eucapliptos of the parroquia san jua, municipio libertador

Las enfermedades cardiovasculares y el síndrome metabólico son patologías que afectan a gran parte de la población mundial, de etiología poligénica y multifactorial, resultado de la interacción entre factores genéticos, ambientales, sociales y culturales. Los principales genes candidatos a estudiar son aquellos relacionados con la regulación de la homeostasis de la glucosa, del metabolismo lipídico y/o de la secreción y acción de la insulina, como son el gen de los Receptores de los Proliferadores Perixosomales Activados gamma 2 (PPARγ2), la Proteína Enlazante de Ácidos Grasos Intestinal (FABP2) y la Apolipoproteína E (ApoE). Evaluar la relación entre los polimorfismos Pro12Ala del gen PPARγ2, Ala54Thr del gen FABP2 y del gen de ApoE en habitantes del Sector “Los Eucaliptos” de la Parroquia San Juan. 308 individuos de dicha comunidad, 98 hombres y 210 mujeres, clasificados en hipercolesterolémicos, hipertrigliceridémicos, resistentes a la insulina y controles de acuerdo a sus niveles de colesterol total, triglicéridos e índice HOMA. Extracción de 10 mL de sangre venosa para la determinación de química sanguínea y extracción de ADN, amplificación mediante PCR de un fragmento de 102pb del gen de PPARγ2, uno de 180pb del gen de FABP2 y otro de 244pb del gen de ApoE, y posterior RFLP. Se encontró una frecuencia alélica de 0,91 para el alelo Pro y 0,09 para el Ala del gen de PPARγ2; 0,70 para el alelo Ala del gen FABP2 y 0,30 para el Thr, mientras que para los alelos del gen de ApoE la frecuencia fue de ε2=0,05, ε3=0,80 y ε4=0,15. Se encontró relación entre el alelo ε4 de ApoE y la hipercolesterolemia, además del alelo ε2 como factor protector ante el desarrollo de hipercolesterolemia, hipertrigliceridemia y resistencia a la insulina, no encontrándose asociación alguna entre los polimorfismos de los restantes genes y las patologías mencionadas.

Cardiovascular disease and metabolic syndrome are diseases that affect worldwide, with multiple genetic and environmental components contributing to susceptibility. The main candidate genes to study are those related to the regulation of glucose homeostasis, lipid metabolism, insulin secretion and action and obesity, these include the genes for Peroxisome proliferator-activated receptor gamma 2 (PPARγ2), fatty acid-binding protein 2 (FABP2) and Apolipoprotein E (Apo E). The aim of this study was to investigate the relationship between polymorphisms of Pro12Ala PPARγ2 gene, Ala54Thr FABP2 gene and the ApoE gene in residents from the “The Eucaliptus” of the “Parroquia San Juan”. 308 subjects, 98 men and 210 women, classified as hypercholesterolemic, hypertriglyceridemic, insulin resistant and controls according to their levels of total cholesterol, triglycerides and HOMA index. Extraction of 10 mL whole blood for determination of chemistry and DNA extraction, PCR amplification of a 102 bp fragment PPARγ2 gene, a 180 bp FABP2 gene and a 244 bp of ApoE gene, and subsequent RFLP. An allele frequency for allele Pro 0.91 and 0.09 for gene PPARγ2 Ala and 0.70 for the allele of the gene FABP2 Ala and 0.30 for Thr, while for the different alleles of ApoE gene frequency was ε2=0.05, ε3=0.80 and ε4=0.15. We found a relationship between the ApoE ε4 allele and hypercholesterolemia, in the other hand, Apo E ε2 allele was found as a protective factor against the development of hypercholesterolemia, hypertriglyceridemia and insulin resistance, we did not found association between polymorphisms of the other genes and the pathologies mentioned above.

Effect of globular domain of adiponectin on glucose metabolism and insulin signal transduction in insulin resistant model adipocytes / 中华内分泌代谢杂志

Insulin resistance model of 3T3-L1 adipocytes were prepared with plamotic acid.Adipocytes with generated insulin resistance were cultured with different concentrations of globular domain of adiponectin(gAd:250,500,1 000 ng/ml).The cell culture medium glucose content was detected with the glucose oxidase method,the mRNA expressions of insulin receptor substrate-1 (IRS-1),phosphatidylinositol-3 kinase(PI3K),and protein kinase B(PKB) were detected with real-time quantitative PCR method.The phosphorylation of IRS-1 was detected by Western blot.Compared with the control group,the experimental group showed significantly increased glucose consumption (P ＜ 0.01),and with the increasing gAd concentration,glucose consumption was gradually increasing.IRS-1 phosphorylation was increased gradually with the increasing concentration of gAd.These results suggest that gAd can promote glucose uptake by 3T3-L1 adipocyte model with generated insulin resistance.This may be correlated with promoting insulin signal transduction and improving insulin resistance in adipocytes.

Uso de la metformina en el tratamiento de pacientes infértiles con síndrome de ovarios poliquísticos / Use of metformin in the treatment of infertile patients with polycystic ovary syndrome

Determinar el efecto de la terapia con metformina en pacientes infértiles con síndrome de ovarios poliquísticos. Estudio clínico, prospectivo y descriptivo. Incluyó pacientes con diagnóstico de síndrome de ovarios poliquísticos, infertilidad y resistencia a la insulina, a las que se les administró tratamiento con metformina por 3 meses. Las pacientes que no se embarazaron en ese período recibieron tratamiento con citrato de clomifeno, hasta un máximo de 6 meses. En el Servicio de Fertilidad Maternidad "Concepción Palacios". Caracas. Resultados: Se completó un total de 62 pacientes. La tasa de embarazo de 25,8 por ciento (19 pacientes). Un 57,9 por ciento de las pacientes lograron embarazo con 3 meses de tratamiento, con una P= 0,492 lo cual no fue estadísticamente significante. La tasa de embarazos con citrato de clomifeno fue de 23,5 por ciento (8 pacientes), P=0,684. El 63,2 por ciento (12) tuvo un embarazo a término. La tasa de aborto fue de 26,3 por ciento (5). La metformina induce ovulación espontánea en pacientes con síndrome de ovarios poliquísticos. No existe diferencia estadística entre la tasa de embarazos con la terapia con metformina sola y metformina con citrato de clomifeno. La metformina mejora la evolución de embarazo

To determine the effect of treatment with metformin in infertile patients with polycystic ovary syndrome. Clinical, prospective and descriptive study. Infertile anovulatory patients with polycystic ovary syndrome and insulin resistant were included, and all of them, were treated with metformin for 3 months. Patients who did not ovulate in this time, received clomiphene citrate for 6 months. Fertility Service of Maternidad "Concepcion Palacios". 62 infertile patients were included in this study. The pregnancy rate was 25.8 percent (19 patients). The 57.9 percent of women became pregnant with metformin administration for 3 months, with P= 0.492, it was not statistical significance. The pregnancy rate with clomiphene citrate was 23.5 percent (8 patients), P= 0.684. The abortion rate was 26.3 percent (5). The metformin induce ovulation in anovulatory polycystic ovary syndrome women, whereas the pregnancy rate resulted similar in both treatment groups: metformin alone and metformin and clomiphene citrate

Clinical Investigation of Lower-extremity Arterial Disease in Patients with Newly Diagnosed Type 2 Diabetes Mellitus Combined with Nonalcoholic Fatty Liver Disease / 中山大学学报(医学科学版)

[Objective] To investigate the clinical characteristics and risk factors of lower-extremity arterial disease in the patients with newly diagnosed type 2 diabetes mellitus combined with nonalcoholic fatty liver disease (NAFLD). [Methods] One hundred fifty-one patients were investigated respectively. The patients were divided into two groups (NAFLD-Group and non-NAFLD group) by liver ultrasonography and disease history, then their clinical data were collected and compared in order to find the differences of biochemical indicators and the morbidity of lower-extremity arterial disease between two groups. [Results] Ninety-two cases (60.93%) were complicated with NAFLD. NAFLD group had higher levels of fast insulin and C peptide level, postprandial insulin and C peptide level, uric acid, body mass index (BMI), homeostasis model assessment (HOMA-IR) and lower level of high-density lipoprotein cholesterol and insulin sensitive index than those of without NAFLD (P<0.05). One hundred and one cases(66.89%) were complicated with lower-extremity arterial disease. The morbidity of lower-extremity arterial diseases was higher in NAFLD group than that of without NAFLD group (75% vs. 54.24%, P<0.01). [Conclusion] Both lower-extremity arterial disease and NAFLD are common complicated with type 2 diabetes. The morbidity of lower-extremity arterial diseases was higher in NAFLD group than that of without NAFLD group.

Effects of exercises on expressions of retinol binding protein-4 in serum and phosphatidylinositol 3 kinase in skeletal muscles of insulin resistant rats / 中华物理医学与康复杂志

Objective To investigate the effects of exercises on expressions of retinol binding protein-4 (RBP4)in serum and phosphatidylinositol 3 kinase(PI3K)in skeletal muscles of insulin-resistant(IR)rats induced by diets.Methods A total of 30 Wistar rats were randomly divided into 3 groups:normal control group fed with normal diet,IR and exercises groups with high sugar and high fat diet.After 8 weeks,the Wistar rats in exercises group took swimming training for 6 weeks and all groups kept their assigned diets.At the end of 14-week experiment,the body weight(BW)of rats were measured,the general behaviors of rats were observed and then sacrificed.Rats' blood were sampled for measuring the levels of glucose(FPC)and serum RBP4,insulin(FINS),HDL-C,LDL-C,TG,TC.The indexes of IR(HOMA-IR)were calculated.The levels of RBP4 in serum were measured with ELISA technique.The ratios of visceral fat content to BW were calculated too.Immunohistochemistry method was applied to detect the expression levels of PI3K in skeletal muscle.Results(1)The levels of RBP4,TC,TG,FPG in serum in exercises group were lower than those in IR group significantly;the visceral fat content,ratio of visceral fat content to BW,FINS,RBP4,LDL and HOMA-IR in serum increased significantly in IR group after 6 weeks feeding compared with normal control group and exercises group(P＜0.01);the levels of HDL in serum in IR group were lower than those in the other two groups.(2)The expression levels of PI3K in skeletal muscles in exercises group were significantly higher than that in IR group(P＜0.01).(3)In a multiple stepwise regression analysis,FINS,ratio of visceral fat content to BW,LDL and HOMA-IR were correlated with RBP4 positively;HDL and PI3K were correlated with RBP4 negatively.Conclusion Exercises could downregulate the level of RBP4 in serum and upregulate the level of PI3K in skeletal muscles of IR rats.This effect was important for improving the organism sensibility to insulin.

A proteomic study on the insulin resistant HepG_2 cell treated by Ecdysterone / 中国药理学通报

Aim To screen the express-altered proteins before or after effect of Ecdysterone on HepG_2 cell model of insulin resistance by the strategy of comparative proteomics, which may approach new proves exploring the target of sensitizer.Methods HepG_2 cells were incubated with 5×10~(-7) mol·L~(-1) insulin for 16 h, and glucose consumption was determined. After treatment, the insulin resistant cells were incubated with 10~(-5) mol·L~(-1) Ecdysterone for 24 h.Then glucose consumption contents were determined. The proteins of two groups before and after treatment with Ecdysterone were extracted by lysis buffers. The express-altered proteins were screened by 2-DE technique.Some of them were analyzed by MALDI-TOF-MS mass spectrometry and MS-Fit database.Results 53 express-altered protein spots of insulin resistant HepG_2 cells before and after treated by Ecdysterone were screened by 2-DE technique,in which 35 ones were up-regulated and the others down-regulated, 6 spots of which were analyzed by MALDI-TOF-MS mass spectrometry and MS-Fit database.Conclusion The target of Ecdysterone as a sensitizer involves many proteins and kinases which correlate insulin resistant. These results lay a foundation for further studies on the function of these target proteins.

A study on the relationship between serum resistin and insulin resistance in the elderly patients with diabetes / 中华老年医学杂志

Objective To find out the relationship between the serum resistin levels and obesity, insulin sensitivity, blood-glucose as well as blood lipid in the elderly with diabetes. Methods Senile patients (51) suffering from type 2 diabetes and non-diabetic controls(42) were selected. Their serum resistin levels after an overnight fasting were measured by competitive ELISA. Other data including fasting blood-glucose, insulin, blood lipid, insulin sensitivity index, waistline, hipline and WHR were measured. Results (1)In non-diabetic controls, fasting resistin level was significantly higher in obese subjects than that in those persons with normal weight (P

Insulin resistant animal model established by high fat diet / 中国药理学通报

High fat diet is one of the important factors leading to type 2 diabetes mellitus and insulin resistant symptom.Developing a steady and applied model using high-fat diet-fed animals becomes an important part of type 2 diabetes mellitus and insulin resistant symptom researches.Whether high fat diet leads to insulin resistant symptom in experimental animals depends on the following factors: the artifactitious pattern and the fat proportion of the feed,the total amount of calories absorbed by the experimental animal,the duration of the animal model development,the breed and gender of experimental animals and the assistant medicament etc.

EXPRESSION OF ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 IN HUMAN OVARY AND ITS RELATIONSHIP WITH POLYCYSTIC OVARY SYNDROME / 解剖学报

Objective Insulin resistance is a possible cause of polycystic ovary syndrome(PCOS).It is presumed that ectonucleotide pyrophosphatase/phosphodiesterase 1(ENPP1) is associated with insulin resistance.The purpose of this study is to explore the expression of ENPP1 in granulosa cells of the ovary and its relationship with PCOS. Methods Twelve aliquots of follicular granulosa cells were isolated from 12 samples of the patients with PCOS and 22 aliquots from 22 samples of the patients without PCOS,respectively.ENPP1 expression was analyzed by reverse transcription polymerase chain reaction(RT-PCR) and in situ hybridization.The relative expression of ENPP1 mRNA was detected by real-time quantitative polymerase chain reaction(real-time PCR). Results ENPP1 was expressed in granulosa cells of the ovary.ENPP1 expression's 2~(-?Ct) in granulosa cells of PCOS was significantly higher than non-PCOS(1.67?0.89 vs.0.94?0.76,P=0.017).Conclusion ENPP1 expression plays a role in ovary function and may be closely associated with the development of PCOS.