scholarly journals Eleutheroside E, An Active Component ofEleutherococcus senticosus, Ameliorates Insulin Resistance in Type 2 Diabetic db/db Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Jiyun Ahn ◽  
Min Young Um ◽  
Hyunjung Lee ◽  
Chang Hwa Jung ◽  
Seok Hyun Heo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Serum Insulin ◽  
Principal Component ◽  
C2c12 Myotubes ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Eleutheroside E ◽  
Type 2 Diabetic

Eleutheroside E (EE), a principal component ofEleutherococcus senticosus(ES), has anti-inflammatory and protective effects in ischemia heart. However, it is unknown whether it ameliorates insulin resistance and reduces hyperglycemia in diabetes. This study investigated the effect of EE-containing ES extracts, as well as EE, on hyperglycemia and insulin resistance in db/db mice. EE increased the insulin-provoked glucose uptake in C2C12 myotubes. Moreover, EE improved TNF-α-induced suppression of glucose uptake in 3T3-L1 adipocytes. Five-week-old db/db mice were fed a diet consisting of ES extract or EE for 5 weeks. Both were effective in improving serum lipid profiles and significantly decreased blood glucose and serum insulin levels. ES and EE supplementation effectively attenuated HOMA-IR. Glucose tolerance and insulin tolerance tests showed that EE increased insulin sensitivity. Immunohistochemical staining indicated that ES and EE protected pancreatic alpha and beta cells from diabetic damage. In addition, ES and EE improved hepatic glucose metabolism by upregulating glycolysis and downregulating gluconeogenesis in obese type 2 diabetic mice. These data suggest that EE mediates the hyperglycemic effects of ES by regulating insulin signaling and glucose utilization. The beneficial effects of EE may provide an effective and powerful strategy to alleviate diabetes.

scholarly journals Trilobatin Ameliorates Insulin Resistance through IRS-AKT-GLUT4 Signaling Pathway in C2C12 Myotubes and ob/ob Mice

2020 ◽  
Author(s):  
Min Liu ◽  
Lujing Wang ◽  
Xigan Li ◽  
Yucui Wu ◽  
Fei Yin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Fasting Blood Glucose ◽  
C2c12 Myotubes ◽  
Peripheral Tissues ◽  
Resistance Protein ◽  
Type 2 Diabetic

Abstract Background: Trilobatin, a natural compound, has been found to exhibit anti-diabetic properties in high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic mice. But up to now no research has been reported on the effect of trilobatin on insulin resistance in peripheral tissues. Herein, we determined the effects of trilobatin on insulin resistance in palmitate-treated C2C12 myotubes and ob/ob mice.Methods: 8-10 weeks of male ob/ob mice and same background C57BL/6 mice were used to evaluate the role of trilobatin on insulin resistance; Protein expression and phosphorylation were measured by western blot; Glucose uptake was determined a fluorescent test.Results: treatment with trilobatin prevented palmitate-induced insulin resistance by enhancing glucose uptake and the phosphorylation of IRS1 and AKT, recovered the translocation of GLUT4 from cytoplasm to membrane, but preincubation with LY294002, an inhibitor of PI3K, blocked the effects of trilobatin on glucose uptake and the distribution of GLUT4 in C2C12 myotubes. Furthermore, administration with trilobatin for 4 weeks significantly improved insulin resistance by decreasing fasting blood glucose and insulin in serum, enhancing the phosphorylation of IRS1 and AKT, and recovering the expression and translocation of GLUT4 in ob/ob mice.Conclusions: IRS-AKT-GLUT4 signaling pathway might be involved in trilobatin ameliorating insulin resistance in skeletal muscle of obese animal models.

scholarly journals Trilobatin ameliorates insulin resistance through IRS-AKT-GLUT4 signaling pathway in C2C12 myotubes and ob/ob mice

2020 ◽  
Author(s):  
Min Liu ◽  
Lujing Wang ◽  
Xigan Li ◽  
Yucui Wu ◽  
Fei Yin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Fasting Blood Glucose ◽  
C2c12 Myotubes ◽  
Peripheral Tissues ◽  
Resistance Protein ◽  
Type 2 Diabetic

Abstract Background: Trilobatin, a natural compound, has been found to exhibit anti-diabetic properties in high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic mice. But up to now no research has been reported on the effect of trilobatin on insulin resistance in peripheral tissues. Herein, we determined the effects of trilobatin on insulin resistance in palmitate-treated C2C12 myotubes and ob/ob mice.Methods: 8-10 weeks of male ob/ob mice and same background C57BL/6 mice were used to evaluate the role of trilobatin on insulin resistance; Protein expression and phosphorylation were measured by western blot; Glucose uptake was determined a fluorescent test.Results: treatment with trilobatin prevented palmitate-induced insulin resistance by enhancing glucose uptake and the phosphorylation of insulin resistance substrate 1 (IRS1) and protein Kinase B, (PKB/AKT), recovered the translocation of GLUT4 from cytoplasm to membrane, but preincubation with LY294002, an inhibitor of PI3K, blocked the effects of trilobatin on glucose uptake and the distribution of GLUT4 in C2C12 myotubes. Furthermore, administration with trilobatin for 4 weeks significantly improved insulin resistance by decreasing fasting blood glucose and insulin in serum, enhancing the phosphorylation of IRS1 and AKT, and recovering the expression and translocation of GLUT4 in ob/ob mice.Conclusions: IRS-AKT-GLUT4 signaling pathway might be involved in trilobatin ameliorating insulin resistance in skeletal muscle of obese animal models.

scholarly journals Trilobatin ameliorates insulin resistance through IRS-AKT-GLUT4 signaling pathway in C2C12 myotubes and ob/ob mice

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Min Liu ◽  
Lujing Wang ◽  
Xigan Li ◽  
Yucui Wu ◽  
Fei Yin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Fasting Blood Glucose ◽  
C2c12 Myotubes ◽  
Peripheral Tissues ◽  
Resistance Protein ◽  
Type 2 Diabetic

Abstract Background Trilobatin, a natural compound, has been found to exhibit anti-diabetic properties in high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic mice. But up to now no research has been reported on the effect of trilobatin on insulin resistance in peripheral tissues. Herein, we determined the effects of trilobatin on insulin resistance in palmitate-treated C2C12 myotubes and ob/ob mice. Methods Male ob/ob mice (8-10 weeks) and same background C57BL/6 mice were used to evaluate the role of trilobatin on insulin resistance; protein expression and phosphorylation were measured by western blot; glucose uptake was determined a fluorescent test. Results Treatment with trilobatin prevented palmitate-induced insulin resistance by enhancing glucose uptake and the phosphorylation of insulin resistance substrate 1 (IRS1) and protein Kinase B, (PKB/AKT), recovered the translocation of GLUT4 from cytoplasm to membrane, but preincubation with LY294002, an inhibitor of PI3K, blocked the effects of trilobatin on glucose uptake and the distribution of GLUT4 in C2C12 myotubes. Furthermore, administration with trilobatin for 4 weeks significantly improved insulin resistance by decreasing fasting blood glucose and insulin in serum, enhancing the phosphorylation of IRS1 and AKT, and recovering the expression and translocation of GLUT4 in ob/ob mice. Conclusions IRS-AKT-GLUT4 signaling pathway might be involved in trilobatin ameliorating insulin resistance in skeletal muscle of obese animal models.

scholarly journals Reducing effect of insulin resistance on alpha-synuclein gene expression in skeletal muscle

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Amirhosein Khoshi ◽  
Golnaz Goodarzi ◽  
Rezvan Mohammadi ◽  
Roghaye Arezumand ◽  
Meysam Moghbeli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Glucose Uptake ◽  
Alpha Synuclein ◽  
C2c12 Cells ◽  
Diabetic Mice ◽  
Insulin Metabolism ◽  
Insulin Resistant ◽  
Type 2 Diabetic

Abstract Background Alpha-synuclein (SNCA) as the presynaptic protein is expressed in different tissues and prevents insulin-resistance (IR) through increasing glucose-uptake by adipocytes and muscles. However, the effect of insulin metabolism on SNCA expression has scarcely elucidated. In present study we assessed the probable effect of insulin resistance on SNCA expression in muscle C2C12 cells and also skeletal muscle tissues of type 2 diabetic mice. Materials and methods Sixteen male C57BL/6 mice were divided into two experimental groups, including control and type 2 diabetic mice with IR (induced by high-fat diet + low-dose streptozotocin). The animals of the study involved the measurements of fasting blood glucose, oral-glucose-tolerance-test, as well as fasting plasma insulin. Moreover, insulin-resistant and insulin-sensitive muscle C2C12 cells were prepared. The insulin-resistance was confirmed by the glucose-uptake assay. Comparative quantitative real time PCR was used to assess the SNCA expression. Results The obtained results have showed a significant ~ 27% decrease in SNCA expression level in muscle tissue of diabetic mice (P = 0.022). Moreover, there was a significant change of SNCA expression in insulin-resistant C2C12 cells (P < 0.001). Conclusion Type 2 diabetes due to insulin-resistance can decrease SNCA gene expression in muscles. In addition to the role of SNCA in cell susceptibility to insulin and glucose uptake, the SNCA expression can also be affected by insulin metabolism.

Anti-inflammatory and insulin secretory activity in experimental type-2 diabetic rats treated orally with magnesium

2018 ◽  
Vol 29 (5) ◽  
pp. 507-514 ◽  
Author(s):  
Abayomi Oluwatosin Ige ◽  
Olanrewaju Amos Ajayi ◽  
Eunice Olufunke Adewoye
Keyword(s):  
Insulin Resistance ◽  
Serum Insulin ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Low Grade ◽  
Control Serum ◽  
Experimental Type ◽  
Anti Inflammatory ◽  
Type 2 Diabetic

Abstract Background Diabetes mellitus causes low-grade chronic inflammation which leads to the development of long-term complications. Oral magnesium (Mg) intake amongst other effects was reported to reduce the levels of inflammatory markers. This study investigated the anti-inflammatory and insulin secretory activities in experimental type-2 diabetic rats (n=32) orally treated with Mg. Methods Experimental type-2 diabetic rats were induced with high fat diet and alloxan (50 mg/kg, single i.p.) for over 10 weeks prior to the experimental procedures. Male Wistar rats were divided into 4 equal groups: control, untreated experimental diabetics, and experimental diabetics treated orally with either metformin (Met) (250 mg/kg), or Mg (250 mg/kg), respectively, for 14 days. The blood glucose (BG) levels were monitored before experimental induction of diabetes and thereafter on days 1, 7, 10, and 14, respectively. Serum insulin, C-reactive protein (CRP), interleukin-6 (IL-6), and lipid profile were assessed using laboratory kits while pancreatic beta cell function (BCF) and insulin resistance were estimated using homeostasis model assessment equations. Results Significant increase in the BG level was observed in all experimental diabetic groups on day 1 compared to controls. On day 14, BG, BCF, triglyceride, cholesterol, and low-density lipoprotein levels were increased while the high-density lipoprotein level was reduced in untreated diabetics compared to other groups. Insulin and insulin resistance were increased in all groups compared to control. Serum insulin and IL-6 were reduced while CRP was elevated in diabetic treated groups (Met and Mg) compared to untreated diabetics. Conclusions This study shows a hypoglycemic, lipid regulatory, insulin stimulatory, and anti-inflammatory effect of oral Mg treatment in experimental type-2 diabetic rats.

scholarly journals Irbesartan Ameliorates Diabetic Nephropathy by Suppressing the RANKL-RANK-NF-κB Pathway in Type 2 Diabetic db/db Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao-Wen Chen ◽  
Xiao-Yan Du ◽  
Yu-Xian Wang ◽  
Jian-Cheng Wang ◽  
Wen-Ting Liu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Glomerular Sclerosis ◽  
Protective Effects ◽  
Podocyte Injury ◽  
Beneficial Effects ◽  
Focal Segmental Glomerular Sclerosis ◽  
Receptor Activator ◽  
Segmental Glomerular Sclerosis ◽  
Type 2 Diabetic

The receptor activator of NF-κB ligand (RANKL) and its receptor RANK are overexpressed in focal segmental glomerular sclerosis (FSGS), IgA nephropathy (IgAN), and membranous nephropathy (MN). However, the expression and the potential roles of RANKL and RANK in diabetic nephropathy (DN) remain unclear. Irbesartan (Irb) has beneficial effects against diabetes-induced renal damage, but its mechanisms are poorly understood. Our present study investigated the effects of Irb in DN and whether the renal protective effects of Irb are mediated by RANKL/RANK and the downstream NF-κB pathway in db/db mice. Our results showed that db/db mice revealed severe metabolic abnormalities, renal dysfunction, podocyte injury, and increased MCP-1; these symptoms were reversed by Irb. At the molecular level, RANKL and RANK were overexpressed in the kidneys of db/db mice and Irb downregulated RANKL and RANK and inhibited the downstream NF-κB pathway. Our study suggests that Irb can ameliorate DN by suppressing the RANKL-RANK-NF-κB pathway.

scholarly journals Protective effects of calorie restriction on insulin resistance and islets function in STZ-induced type 2 diabetes rats

2020 ◽  
Author(s):  
Li Zhang ◽  
Ying-juan Huang ◽  
Jia-pan Sun ◽  
Ting-ying Zhang ◽  
Tao-li Liu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Uptake ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Chow Diet ◽  
Protective Effects ◽  
Insulin Tolerance ◽  
Calorie Diet

Abstract Background Caloric restriction (CR), as the only approved scientific method that can retard aging, has become more and more attractive in the treatment of type 2 diabetes mellitus (T2DM) due to increasingly common high calorie diet and sedentary lifestyle. This study aimed to evaluate its role in T2DM treatment and further explored the potential molecular mechanism.Methods A total of 60 male SD rats were used in this study. Diabetes model was induced by 8 weeks of high-fat diet (HFD) followed by a single dose of streptozotocin injection (30mg/kg). Subsequently, the diabetic rats were fed ab libitum of 28g/day (diabetic control) or 20g/day (30% CR regimen) with HFD for 20 weeks. Meanwhile, normal rats had free standard chow diet served as vehicle control. Body mass, plasma glucose, and lipid profile were monitored. After diabetes-related functional tests being done, rats were sacrificed at 10 and 20 weeks, and glucose uptake in fresh muscle were determined. Liver and pancreas were prepared for histopathology and histochemical evaluations, and western blotting and immunofluorescence were applied to detect alterations in AKT/AS160/GLUT4 signaling. Results 30% CR significantly attenuated hyperglycemia and dyslipidemia, leading to alleviation of glucolipotoxicity, thus protected islets secretion, retarding the exhaustion of islets function. Insulin resistance was also markedly ameliorated, as indicated by notably improved insulin tolerance and HOMA-IR. However, glucose uptake in skeletal muscle was not significantly improved, and the up-regulation of AKT/AS160/GLUT4 signaling in muscle induced by 30% CR attenuated gradually over time. However, the consecutive decrease in AKT/AS160/GLUT4 signaling in white adipose tissue was significantly reversed by 30% CR. Conclusion 30% CR could protect islets function from hyperglycemia and dyslipidemia, and improve insulin resistance with probable mechanism related to the up-regulation of AKT/AS160/GLUT4 signaling.

scholarly journals Regulation of MicroRNA 103 and 107 in Obese T2DM Patients Maintained on Metformin

2021 ◽  
Author(s):  
Nahla E. El-Ashmawy ◽  
Amr M. Gawaly ◽  
Hala A. EL Batanony ◽  
Naglaa F. Khedr
Keyword(s):  
Insulin Resistance ◽  
Serum Insulin ◽  
Glycosylated Hemoglobin ◽  
Serum Levels ◽  
Diabetic Control ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Diagnostic Biomarkers ◽  
Type 2 Diabetic

Abstract Metformin increases insulin sensitivity in obese type 2 diabetic patients (T2DM) by different mechanisms. The current study was conducted to estimate the levels of miRNA-103 and 107 in obese non diabetic subjects as well as obese T2DM patients maintained on metformin, and to correlate between the levels of miR 103 and 107 and the development of insulin resistance. Ninety subjects were equally recruited into three groups; obese non diabetic control (OC), obese newly diagnosed diabetic (ONDD) and obese type 2 diabetic treated with metformin (MetD). Serum levels of blood glucose, insulin, lipid profile, glycosylated hemoglobin (HbA1c), miR103&107 expression and DICER-1 were analyzed. Serum levels of HbA1c, FBG, HOMA-IR, T.ch, TG, LDL-C and VLDL-C were increased in ONDD (p˂0.0001) compared to OC and MetD. Significant increase of HDL-C (p = 0.022) was observed in MetD compared to OC and ONDD. Serum insulin was increased (p = 0.004) and miR 103 & 107 gene expression (p < 0.0001) in ONDD and significant down-regulation in MetD compared to OC group. DlCER-1 levels were decreased (p < 0.0001) in ONDD group and increased in MetD group compared to OC group. Both miR 103 and 107 were positively correlated with insulin and HOMA-IR, but negatively correlated with DICER-1. Depending on the estimated cutoff-values of area under receiver curve (AUC), miR 103 and 107 were excellent diagnostic biomarkers for insulin resistance. Our findings indicated the clinical utility of miR103 and miR 107 in diagnosis and treatment of insulin resistance. Moreover, metformin can affect miR 103 and miR 107 through modulation of DICER-1 level.

scholarly journals Protective effects of calorie restriction on insulin resistance and islets function in STZ-induced type 2 diabetes rats

2021 ◽  
Author(s):  
Li Zhang ◽  
Ying-juan Huang ◽  
Jia-pan Sun ◽  
Ting-ying Zhang ◽  
Tao-li Liu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Uptake ◽  
Molecular Mechanisms ◽  
Chow Diet ◽  
Islet Function ◽  
Model Assessment ◽  
Protective Effects ◽  
Sprague Dawley

Abstract Background Caloric restriction (CR) has become increasingly attractive in the treatment of type 2 diabetes mellitus (T2DM) because of the increasingly common high-calorie diet and sedentary lifestyle. This study aimed to evaluate the role of CR in T2DM treatment and further explore its potential molecular mechanisms.Methods Sixty male Sprague-Dawley rats were used in this study. The diabetes model was induced by 8 weeks of high-fat diet (HFD) followed by a single dose of streptozotocin injection (30 mg/kg). Subsequently, the diabetic rats were fed HFD at 28 g/day (diabetic control) or 20 g/day (30% CR regimen) for 20 weeks. Meanwhile, normal rats fed a free standard chow diet served as the vehicle control. Body mass, plasma glucose levels, and lipid profiles were monitored. After diabetes-related functional tests were performed, the rats were sacrificed at 10 and 20 weeks, and glucose uptake in fresh muscle was determined. In addition, western blotting and immunofluorescence were used to detect alterations in AKT/AS160/GLUT4 signaling. Results We found that 30% CR significantly attenuated hyperglycemia and dyslipidemia, leading to alleviation of glucolipotoxicity and thus protection of islet function. Insulin resistance was also markedly ameliorated, as indicated by notably improved insulin tolerance and homeostatic model assessment for insulin resistance (HOMA-IR). However, the improvement in glucose uptake in skeletal muscle was not significant. The upregulation of AKT/AS160/GLUT4 signaling in muscle induced by 30% CR also attenuated gradually over time. Interestingly, the consecutive decrease in AKT/AS160/GLUT4 signaling in white adipose tissue was significantly reversed by 30% CR. Conclusion CR (30%) could protect islet function from hyperglycemia and dyslipidemia, and improve insulin resistance. The mechanism by which these effects occurred is likely related to the upregulation of AKT/AS160/GLUT4 signaling.

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