scholarly journals Modulation and bioinformatics screening of hepatic mRNA-lncRNAs (HML) network associated with insulin resistance in prediabetic and exercised mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Fatemeh Kazeminasab ◽  
Sayed Mohammad Marandi ◽  
Maryam Baharlooie ◽  
Mohammad Hossein Nasr-Esfahani ◽  
Kamran Ghaedi
Keyword(s):  
Insulin Resistance ◽  
Expression Patterns ◽  
Diabetic Mice ◽  
Mice Model ◽  
Prediabetic State ◽  
Hepatic Expression ◽  
Potential Association ◽  
Resistance Pathway ◽  
Python Programming

Abstract Background Insulin resistance is associated with prediabetes and further progression to type 2 diabetes mellitus (T2DM). This study aims to investigate novel hepatic lncRNAs associated with key genes in insulin resistance in prediabetes. Methods In the bioinformatics phase, we have collected screened a pool of lncRNAs and mRNAs according to their potential association to prediabetic condition. We performed pathway analysis of mRNAs, using DAVID tool based on KEGG repository data. Then, we used Python programming language to get a subset of lncRNAs located in 50 kb proximity with high-fat (HF)-responsive mRNAs. In the experimental phase, prediabetic mice model was established by the treatment of HF diets for 12 weeks. After this treatment, HF-fed animals were divided into two groups of endurance exercised or sedentary, both continuing on the HF diet for 8 weeks. Besides, a group of diabetic mice was treated using a HF diet for 8 weeks followed by injection with STZ solution and then a HF diet for another 4 weeks. Results We found three genes having paired lncRNAs annotated in insulin resistance pathway. Their hepatic expression levels were altered in prediabetic condition as upregulation of Srebf1 was associated with GM38501, upregulation of Pck1 was associated with Ctcflos and GM36691, downregulation of Cpt1b was associated with GM44502. All of these expression patterns were replicated in diabetic mice, correlated positively with their predicted lncRNAs. Interestingly, exercise reversed their expression patterns. Conclusions We suggest that the expression pattern of the hepatic mRNA-lncRNA (HML) network in prediabetic state undergoes similar modification to that of diabetes.

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 Feed-forward signaling of TNF-α and NF-κB via IKK-β pathway contributes to insulin resistance and coronary arteriolar dysfunction in type 2 diabetic mice

2009 ◽  
Vol 296 (6) ◽  
pp. H1850-H1858 ◽  
Author(s):  
Jiyeon Yang ◽  
Yoonjung Park ◽  
Hanrui Zhang ◽  
Xiangbin Xu ◽  
Glen A. Laine ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Expression ◽  
Sodium Nitroprusside ◽  
Protein Modification ◽  
Nuclear Factor Κb ◽  
Diabetic Mice ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

We hypothesized that the interaction between tumor necrosis factor-α (TNF-α)/nuclear factor-κB (NF-κB) via the activation of IKK-β may amplify one another, resulting in the evolution of vascular disease and insulin resistance associated with diabetes. To test this hypothesis, endothelium-dependent (ACh) and -independent (sodium nitroprusside) vasodilation of isolated, pressurized coronary arterioles from mLepr db (heterozygote, normal), Lepr db (homozygote, diabetic), and Lepr db mice null for TNF-α ( dbTNF−/ dbTNF−) were examined. Although the dilation of vessels to sodium nitroprusside was not different between Lepr db and mLepr db mice, the dilation to ACh was reduced in Lepr db mice. The NF-κB antagonist MG-132 or the IKK-β inhibitor sodium salicylate (NaSal) partially restored nitric oxide-mediated endothelium-dependent coronary arteriolar dilation in Lepr db mice, but the responses in mLepr db mice were unaffected. The protein expression of IKK-α and IKK-β were higher in Lepr db than in mLepr db mice; the expression of IKK-β, but not the expression of IKK-α, was attenuated by MG-132, the antioxidant apocynin, or the genetic deletion of TNF-α in diabetic mice. Lepr db mice showed an increased insulin resistance, but NaSal improved insulin sensitivity. The protein expression of TNF-α and NF-κB and the protein modification of phosphorylated (p)-IKK-β and p-JNK were greater in Lepr db mice, but NaSal attenuated TNF-α, NF-κB, p-IKK-β, and p-JNK in Lepr db mice. The ratio of p-insulin receptor substrate (IRS)-1 at Ser307 to IRS-1 was elevated in Lepr db compared with mLepr db mice; both NaSal and the JNK inhibitor SP-600125 reduced the p-IRS-1-to-IRS-1 ratio in Lepr db mice. MG-132 or the neutralization of TNF-α reduced superoxide production in Lepr db mice. In conclusion, our results indicate that the interaction between NF-κB and TNF-α signaling induces the activation of IKK-β and amplifies oxidative stress, leading to endothelial dysfunction in type 2 diabetes.

scholarly journals Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

2015 ◽  
Vol 309 (1) ◽  
pp. E45-E54 ◽  
Author(s):  
Minglong Shao ◽  
Lechu Yu ◽  
Fangfang Zhang ◽  
Xuemian Lu ◽  
Xiaokun Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Combination Treatment ◽  
Combined Treatment ◽  
Protective Effects ◽  
Diabetic Mice ◽  
Renal Protection ◽  
Glucose Levels

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways.

scholarly journals ID: 1080 Adipose-derived stem cells alleviate glucose tolerance in type 2 diabetic mouse

2017 ◽  
Vol 4 (S) ◽  
pp. 166
Author(s):  
Anh Nguyen Tu Bui ◽  
Cong Le Thanh Nguyen ◽  
Anh Thi Minh Nguyen ◽  
Nhat Chau Truong ◽  
Ngoc Kim Phan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Stem Cells ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Adipose Derived Stem Cells ◽  
Diabetic Mice ◽  
Human Ascs ◽  
Type 2 Diabetic

Background: Type 2 diabetes (T2D) is the most common form of diabetes and accounts for 90-95% of all existing diabetic cases. The main etiologies of T2D include insulin resistance in target tissues, insufficient secretion of insulin and subsequent decline of pancreatic β-cell function. Recently, many studies have suggested that adipose – derived stem cells (ASCs) were potential to alleviate insulin resistance and hyperglycemia and promote the islets repair. In this study, ASCs were hypothesized that they could have ameliorative effects on type 2 diabetic mice.  Methods: Type 2 diabetic mice were induced by a combination of high-fat diet and injection of STZ 100 mg/kg and NA 120 mg/kg. Thereafter, two doses of 106 human ASCs were transplanted 2 week interval into each mouse via the tail vein. The mice were monitored health condition, rate of mortaity, body weight, consumption of food and water, blood glucose level, serum insulin level and histological structure of pancreatic islets.  Results: Our results indicated that the ASC-treated mice expressed improved condition in comparision with non-treated diabetic mice. The consumption of food and water as well as the blood glucose level decreased. Simultaneously, ASC transplantation improved the impaired glucose tolerance and insulin tolerance in T2D mice. Besides, the total cholesterol have significantly decreased.  Conclusion: it is suggested that human ASCs infusion is safe and effective for type 2 diabetes mellitus in mice regarding the improved glucose metabolism and insulin resistance.

scholarly journals Beneficial Effects of Poplar Buds on Hyperglycemia, Dyslipidemia, Oxidative Stress, and Inflammation in Streptozotocin-Induced Type-2 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Shiqin Peng ◽  
Ping Wei ◽  
Qun Lu ◽  
Rui Liu ◽  
Yue Ding ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Crude Extract ◽  
Liver Homogenate ◽  
Control Group ◽  
Diabetic Mice ◽  
Model Control

The effects of propolis on blood glucose regulation and the alleviation of various complications caused by diabetes have been widely studied. The main source of propolis in the northern temperate zone is poplar buds. However, there is limited research on the antidiabetic activity of poplar buds. In order to evaluate the effect of poplar buds on type-2 diabetes, crude extract and 50% fraction of poplar buds were used to feed streptozotocin-induced type-2 diabetic mice. The results showed that 50% fraction could increase insulin sensitivity and reduce insulin resistance, as well as decrease the levels of fasting blood glucose, glycated hemoglobin, and glycosylated serum proteins in diabetic mice. Compared with the model control group, the 50% fraction-treated group showed significant decreases of malondialdehyde (MDA) and increases of superoxide dismutase (SOD) in serum and liver homogenate. Moreover, 50% fraction could significantly decrease total cholesterol (TC), alleviate abnormal lipid metabolism, and enhance antioxidant capacity in the serum. For inflammatory factors, feeding of 50% fraction could also reduce the levels of interleukin 6 (IL-6), tumor necrosis factorα(TNF-α), monocyte chemotactic protein 1 (MCP-1), and cyclooxygenase-2 (COX-2) in liver homogenate. Taken together, our results suggest that crude extract and 50% fraction of poplar buds, particularly the latter, can decrease blood glucose levels and insulin resistance, and 50% fraction can significantly relieve dyslipidemia, oxidative stress, and inflammation caused by type-2 diabetes.

From Obesity to Diabetes

2006 ◽  
Vol 76 (4) ◽  
pp. 172-177 ◽  
Author(s):  
Keller
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Free Fatty Acids ◽  
Vegetable Consumption ◽  
Prediabetic State ◽  
The Metabolic Syndrome ◽  
Life Style Changes

The prevalence of obesity has been increasing dramatically in the last decades in the whole world, not only in industrialized countries but also in developing areas. A major complication of obesity is insulin resistance and type 2 diabetes. Diabetes is also rapidly increasing world-wide – reaching a prevalence in adults of approx. 5–6% in Central Europe and in the US, and more than 50% in specific, genetically prone populations. This article reviews pathogenetic mechanisms linking obesity and type 2 diabetes. Emphasis is placed on the observation that excessive amounts of adipocytes are associated with an impairment of insulin sensitivity, a key feature of the "metabolic syndrome". This is a cluster of metabolic abnormalities such as type 2 diabetes, hypertension and dyslipidemia; all of them are enhanced by the presence of visceral (abdominal) obesity and all contribute to the increased cardiovascular risk observed in these patients. Besides release of free fatty acids, adipocytes secrete substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-α and interleukin 6. Increased turnover of free fatty acids interferes with intracellular metabolism of glucose in the muscle, and they exert lipotoxic effect on pancreatic β-cells. The pre-receptor metabolism of cortisol is enhanced in visceral adipose tissue by activation of 11 β-hydroxysteroid dehydrogenase type 1. A new class of anti-diabetic drugs (thiazolidinediones, or glitazones) bind to peroxisome proliferator activated receptor (PPAR-γ) and lower thereby plasma free fatty acids and cytokine production in adipocytes, in addition to a decrease of resistin and an increase in adiponectin observed in animals, resulting in an overall increase in insulin sensitivity and in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance and prevent the development of diabetes should be a reduction in body weight in overweight subjecs, and an increase in physical activity. There are now three published randomized controlled trials demonstrating that in high risk individuals, life style changes with modest weight lost, associated with diminished fat intake and an increase in fruit and vegetable consumption result in marked inhibition of the transition from the prediabetic state to manifest type 2 diabetes.

Abstract 177: Insulin Resistance and Mechanisms of Heart Failure

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Shaodong Guo ◽  
Yajuan Qi ◽  
Qinglei Zhu ◽  
Zihui Xu ◽  
Candice Thomas ◽  
...  
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiac Dysfunction ◽  
Cardiac Fibrosis ◽  
Expression Patterns ◽  
Primary Cultures ◽  
Neonatal Rat ◽  
Atp Content

A major cause of death in patients with type 2 diabetes is cardiac failure and the molecular mechanism that links diabetes to cardiomyopathy remains unclear. Insulin resistance is a hallmark of type 2 diabetes and intensive insulin therapy on the patients with type 2 diabetes increases the risks of cardiovascular dysfunction. Thus, understanding the mechanisms of insulin actions and resistance, related to cardiac dysfunction, will be critical for development of new strategies treating heart failure in type 2 diabetes. Insulin receptor substrate 1, & 2 (IRS1, IRS2) are major components in insulin signaling pathway regulating metabolism and survival. Here we hypothesized that (1) loss of IRS1 and IRS2 causes heart failure; (2) hyperinsulinemia contributes to loss of IRS1 and IRS2 in type 2 diabetes and promotes cardiac dysfunction; and (3) underlying mechanisms are involved in protein kinase activation. H-DKO mice (Heart Double IRS1 and IRS2 Knock-Out) and L(Liver)-DKO mice were generated using Cre/Loxp system. Cardiac function and ATP content were measured by echocardiograms and ATP assay kit. Protein and gene expressions were detected through western-blot and Q-PCR. Primary cultures of neonatal rat ventricular cardiomyocytes (NRVMs) were prepared from Sprague-Dawley rats with enzymatic method. H-DKO mice reduced ventricular mass, developed cardiac fibrosis and failure, and diminished Akt→Foxo1 signaling accompanied by impaired cardiac metabolic gene expression patterns and reduced ATP content. L-DKO mice decreased cardiac expression of IRS1 and IRS2 proteins with insulin resistance, disrupting cardiac energy metabolism, leading to heart failure and activation of p38α MAPK (p38). Using NRVMs, we demonstrated that hyperinsulinemia degraded IRS1 and IRS2, resulting in insulin resistance and impaired insulin action through activation of p38. In conclusion, myocardial loss of IRS1 and IRS2 causes heart failure and is controlled by p38 during Insulin resistance, revealing a fundamental mechanism of heart failure during insulin resistance and/or type 2 Diabetes Mellitus.

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