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.

scholarly journals Exosomes Isolated from Serum of Type 2 Diabetic Mice Increase Proliferation with no Effect on Insulin Stimulated Glucose Uptake of C2C12 Cells

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Christopher Pitzer ◽  
Hector Paez ◽  
Peter Ferrandi ◽  
Junaith Mohamed ◽  
Stephen Alway
Keyword(s):  
Glucose Uptake ◽  
C2c12 Cells ◽  
Diabetic Mice ◽  
Type 2 Diabetic

Increased glucose uptake promotes oxidative stress and PKC-δ activation in adipocytes of obese, insulin-resistant mice

2003 ◽  
Vol 285 (2) ◽  
pp. E295-E302 ◽  
Author(s):  
Ilana Talior ◽  
Merav Yarkoni ◽  
Nava Bashan ◽  
Hagit Eldar-Finkelman
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Glucose Uptake ◽  
Glucose Deprivation ◽  
Insulin Resistant ◽  
Glucose Intake ◽  
Glut1 Expression ◽  
And Oxidative Stress ◽  
Type 2 Diabetic

Increased oxidative stress is believed to be one of the mechanisms responsible for hyperglycemia-induced tissue damage and diabetic complications. In these studies, we undertook to characterize glucose uptake and oxidative stress in adipocytes of type 2 diabetic animals and to determine whether these promote the activation of PKC-δ. The adipocytes used were isolated either from C57Bl/6J mice that were raised on a high-fat diet (HF) and developed obesity and insulin resistance or from control animals. Basal glucose uptake significantly increased (8-fold) in HF adipocytes, and this was accompanied with upregulation of GLUT1 expression levels. Insulin-induced glucose uptake was inhibited in HF adipocytes and GLUT4 content reduced by 20% in these adipocytes. Reactive oxygen species (ROS) increased twofold in HF adipocytes compared with control adipocytes and were largely reduced with decreased glucose concentrations. At zero glucose, ROS levels were reduced to the normal levels seen in control adipocytes. The activity of PKC-δ increased twofold in HF adipocytes compared with control adipocytes and was further activated by H2O2. Moreover, PKC-δ activity was inhibited in HF adipocytes either by glucose deprivation or by treatment with the antioxidant N-acetyl-l-cysteine. In summary, we propose that increased glucose intake in HF adipocytes increases oxidative stress, which in turn promotes the activation of PKC-δ. These consequential events may be responsible, at least in part, for development of HF diet-induced insulin resistance in the fat tissue.

A gene expression signature for insulin resistance

2011 ◽  
Vol 43 (3) ◽  
pp. 110-120 ◽  
Author(s):  
Nicky Konstantopoulos ◽  
Victoria C. Foletta ◽  
David H. Segal ◽  
Katherine A. Shields ◽  
Andrew Sanigorski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Large Scale ◽  
Gene Expression Signature ◽  
Channel Blockers ◽  
Expression Signature ◽  
Insulin Resistant ◽  
Novel Strategy

Insulin resistance is a heterogeneous disorder caused by a range of genetic and environmental factors, and we hypothesize that its etiology varies considerably between individuals. This heterogeneity provides significant challenges to the development of effective therapeutic regimes for long-term management of type 2 diabetes. We describe a novel strategy, using large-scale gene expression profiling, to develop a gene expression signature (GES) that reflects the overall state of insulin resistance in cells and patients. The GES was developed from 3T3-L1 adipocytes that were made “insulin resistant” by treatment with tumor necrosis factor-α (TNF-α) and then reversed with aspirin and troglitazone (“resensitized”). The GES consisted of five genes whose expression levels best discriminated between the insulin-resistant and insulin-resensitized states. We then used this GES to screen a compound library for agents that affected the GES genes in 3T3-L1 adipocytes in a way that most closely resembled the changes seen when insulin resistance was successfully reversed with aspirin and troglitazone. This screen identified both known and new insulin-sensitizing compounds including nonsteroidal anti-inflammatory agents, β-adrenergic antagonists, β-lactams, and sodium channel blockers. We tested the biological relevance of this GES in participants in the San Antonio Family Heart Study ( n = 1,240) and showed that patients with the lowest GES scores were more insulin resistant (according to HOMA_IR and fasting plasma insulin levels; P < 0.001). These findings show that GES technology can be used for both the discovery of insulin-sensitizing compounds and the characterization of patients into subtypes of insulin resistance according to GES scores, opening the possibility of developing a personalized medicine approach to type 2 diabetes.

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.

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