Puerariae Lobatae Radix elevated expression levels of OB-R, IRS2, GLUT1 and GLUT2 to regulate glucose metabolism in insulin-resistance HepG2 cells / 中国中药杂志

To observe the anti-hyperglycemic effect of Puerariae Lobatae Radix in hepatocyte insulin resistance(IR) models, and investigate its preliminary molecular mechanism. IR-HepG2 cell model was stably established with 1×10-9 mol•L⁻¹ insulin plus 3.75×10-6 mol•L-1 dexamethasone treatment for 48 h according to optimized protocol in our research group. After IR-HepG2 cells were treated with different concentrations(5%,10% and 15%) of Puerariae Lobatae Radix-containing serum, cell viability was detected by CCK-8 assay; the glucose consumptions in IR-HepG2 cells were separately detected at different time points (12, 15, 18, 21, 24, 30, 36 h) by using glucose oxidase method; intracellular glycogen content was detected by anthrone method; and the protein expression levels of leptin receptor (Ob-R), insulin receptor substrate-2 (IRS2), glucose transporter 1(GLUT1) and GLUT2 were detected by Western blot assay. The results showed that Puerariae Lobatae Radix-containing serum (5%, 10% and 15%) had no significant effect on IR-HepG2 cell viability; 5% and 10% Puerariae Lobatae Radix-containing serum significantly increased glucose consumption of IR-HepG2 cells (P<0.01) at 18, 21 and 24 h; 15% Puerariae Lobatae Radix-containing serum elevated the glucose consumption of IR-HepG2 cells at 15 h (P<0.05), and significantly elevated the glucose consumption at 18, 21, 24 and 30 h (P<0.01) in a dose-dependent manner. The optimized time of anti-hyperglycemic effect was defined as 24 h, and further study showed that Puerariae Lobatae Radix-containing serum could increase intracellular glycogen content after 24 h treatment (P<0.01), and up-regulate IRS2, Ob-R, GLUT1 and GLUT2 protein expression levels. Our results indicated that Puerariae Lobatae Radix-containing serum could achieve the anti-hyperglycemic effect through important PI3K/PDK signaling pathway partially by up-regulating the expression levels of Ob-R and IRS2, GLUT1 and GLUT2 in IR-HepG2 cells, accelerating the glucose transport into hepatocytes and increasing hepatic glycogen synthesis to enhance the anti-hyperglycemic effect of IR-HepG2 cells.

The FOXO1 Gene-Obesity Interaction Increases the Risk of Type 2 Diabetes Mellitus in a Chinese Han Population

Here, we aimed to study the effect of the forkhead box O1-insulin receptor substrate 2 (FOXO1-IRS2) gene interaction and the FOXO1 and IRS2 genes-environment interaction for the risk of type 2 diabetes mellitus (T2DM) in a Chinese Han population. We genotyped 7 polymorphism sites of FOXO1 gene and IRS2 gene in 780 unrelated Chinese Han people (474 cases of T2DM, 306 cases of healthy control). The risk of T2DM in individuals with AA genotype for rs7986407 and CC genotype for rs4581585 in FOXO1 gene was 2.092 and 2.57 times higher than that with GG genotype (odds ratio [OR] = 2.092; 95% confidence interval [CI] = 1.178–3.731; P = 0.011) and TT genotype (OR = 2.571; 95% CI = 1.404–4.695; P = 0.002), respectively. The risk of T2DM in individuals with GG genotype for Gly1057Asp in IRS2 gene was 1.42 times higher than that with AA genotype (OR = 1.422; 95% CI = 1.037–1.949; P = 0.029). The other 4 single nucleotide polymorphisms (SNPs) had no significant association with T2DM (P > 0.05). Multifactor dimensionality reduction (MDR) analysis showed that the interaction between SNPs rs7986407 and rs4325426 in FOXO1 gene and waist was the best model confirmed by interaction analysis, closely associating with T2DM. There was an increased risk for T2DM in the case of non-obesity with genotype combined AA/CC, AA/AC or AG/AA for rs7986407 and rs4325426, and obesity with genotype AA for rs7986407 or AA for rs4325426 (OR = 3.976; 95% CI = 1.156–13.675; P value from sign test [P(sign)] = 0.025; P value from permutation test [P(perm)] = 0.000–0.001). Together, this study indicates an association of FOXO1 and IRS2 gene polymorphisms with T2DM in Chinese Han population, supporting FOXO1-obesity interaction as a key factor for the risk of T2DM.

Prophylactic efficacy and possible mechanisms of oligosaccharides based standardized fenugreek seed extract on high-fat diet-induced insulin resistance in C57BL/6 mice.

The present work was aimed to study the efficacy and possible mechanism of oligosaccharides based standardized fenugreek seed extract (SFSE-OS) on high-fat diet (HFD)-induced insulin resistance in male C57BL/6 mice. The effects of 12 weeks of oral administration of SFSE-OS (30, 60 and 100 mg/kg, twice daily) were evaluated on HFD fed mice for anthropomorphic, glycemic, gene expression related and histopathological parameters. Separate groups of mice with vehicle co-administered with HFD and low-fat diet (LFD) were maintained as HFD control and LFD control respectively. Twelve weeks of SFSE-OS (60 and 100 mg/kg, p.o.) administration showed significant prophylactic effects on HFD induced insulin resistance in terms of body weight, plasma glucose and insulin levels, glycated hemoglobin, insulin resistance (IR), area under the curve (AUC) of plasma glucose during oral glucose tolerance and intraperitoneal insulin tolerance. Furthermore, HFDinduced mRNA expression changes in adipose tissue, liver and skeletal muscle were prevented by SFSE-OS coadministration. Histology of sections of the pancreas showed the normal architecture in all groups of mice. SFSE-OS showed promising efficacy in prevention of HFD-induced insulin resistance through modulation of Glut-2, Glut-4, IRS-2 and SREBP-1c expression.

Frecuencia del polimorfismo Gly1057Asp del gen IRS-2 en un grupo de la población cubana, y su relación con la diabetes mellitus 2 y el sobrepeso / Frequency of Gly105Asp polymorphism of the IRS-2 gene in a group of the Cuban population: its relation to Type 2 diabetes mellitus and the overweight

La diabetes mellitus tipo 2 es una de las epidemias de mayor impacto a nivel mundial. La susceptibilidad genética constituye un importante factor de riesgo en ella, que se adiciona al efecto de los factores ambientales y al modo de vida. Explorar el papel del polimorfismo Gly1057Asp del gen IRS-2 en la susceptibilidad genética para la diabetes mellitus tipo 2. Se estudió la frecuencia del polimorfismo Gly1057Asp del IRS-2 en 499 ciudadanos cubanos, con IMC³22 y <30, con edades comprendidas entre los 40 y 70 años, de ellos 272 (54,5 por ciento) diabéticos y 227 (45,5 pro ciento) no diabéticos. Para la comparación de las frecuencias de este polimorfismo en ambos grupos utilizamos la prueba chi cuadrado (p<0,05) y para la cuantificación de las asociaciones se utilizó la razón de productos cruzados. La frecuencia del alelo Asp1057 del polimorfismo Gly1057Asp del gen IRS-2 fue de 49,8 por ciento en el grupo de pacientes diabéticos, y de 58,8 por ciento en el grupo de los no diabéticos (p<0,05), lo cual sugiere que este alelo confiere protección contra la diabetes. Sin embargo, este patrón de distribución de frecuencias cambia en personas con sobrepeso, en las que la presencia del alelo Asp1057 llega a asociarse al hiperinsulinismo. En sujetos con antecedentes paternos y/o maternos de diabetes mellitus tipo 2 la acción protectora del alelo Asp1057 no se expresa. En el grupo de la población cubana estudiada el alelo Asp1057 del gen IRS-2 confiere protección para la diabetes mellitus tipo 2. El sobrepeso y los antecedentes maternos y/o paternos de diabetes modifican esta acción protectora(AU)

Type 2 diabetes mellitus is one of the more hard-bitting pandemic at world level. Genetic susceptibility is an important risk factor of it, as well as the effect of environmental factors, and lifestyles. to explore role of Gly1057Asp polymorphism of IRS-2 gene in genetic oversensitivity for Type 2 diabetes mellitus. Frequency of Gly1057Asp polymorphism of IRS-2 gene in was studied in 499 Cuban citizens, with IMC³22 and <30, aged from 40 to 70, of them, 272 (54,5 percent) were diabetic people and 277 (45,5 percent) were non-diabetic. For comparison of frequency of this polymorphism in both groups, we used 2Chi test (p<0,05), and to quantify associations, we used crossed-products ratio. Frequency of Asp1057 allele of Gly1057Asp polymorphism of IRS-2 gene was of 49,8 percent in diabetic patient group, and of 58,8 percent in the group on non-diabetic one (p<0,05), suggesting that this allele confers protection against diabetes. However, this pattern of frequency distribution changes in persons overweighed, in which presence of Asp1057 allele becomes associated with hyperinsulinism. In subjects with family backgrounds of Type 2 diabetes mellitus, protection of Asp1057 allele is not expressed. In group of study Cuban population, Asp1057 allele of IRS-2 gene confers protection against Type 2 diabetes mellitus. Overweight and family backgrounds modify this protective action(AU)

Regulations of acupuncture on hepatic tissue IRS2 gene expression in type 2 diabetes rats / 中华中医药杂志

Objective:To study the relationship between hepatic tissue insulin receptor substrate 2(IRS2) gene and type 2 diabetes,and the regulation of acupuncture on IRS2 gene expression of hepatic tissue in type 2 diabetes mellitus(T2DM) rats.Methods:Obese rats due to diet were injected in abdomen with small dose streptozotocin(STZ) to induce T2DM.Then these T2DM rats were stochastically divided into acupuncture group,Glibenclamide group and model group.After 4 weeks treatment,fasting blood sugar(FBS) was examined with active blood sugar meter,fasting insulin(FINS) was examined by radioimmunoassav,hepatic tissue IRS2mRNA was evaluated in real-time RT PCR,and normal rats were in control.Results:Serum levels of FBS(15.79?1.87) and FINS(37.20?3.92) in model group were higher than those in normal group(5.16?0.13,23.57?1.63),serum levels of FBS(5.46?0.20) and FINS(20.87?1.80) in acupuncture group were obviously lower than those in model group,which were similar to normal group.FBS(5.26?0.13) reduced obviously and serum FINS(28.10?1.86) reduced in some degree in Glibenclamide group compared with model.Relative contents of IRS2mRNA in model group were 2.19 folds compared with that in normal group.And in Glyburide group it was 4.59 folds compared with that in normal group.In acupuncture group it was 4.04% of that in the normal group.Conclusion:Abnormal hepatic tissue IRS2 mRNA expression may be one of pathogenesis of T2DM.Acupuncture can obviously depress hepatic tissue IRS2 mRNA expression,but Glibenclamide can not.