The insulin-signaling pathway of the pancreatic islet is impaired in adult mice offspring of mothers fed a high-fat diet

Nutrition ◽  
2016 ◽  
Vol 32 (10) ◽  
pp. 1138-1143 ◽  
Author(s):  
Isabele Bringhenti ◽  
Fernanda Ornellas ◽  
Carlos Alberto Mandarim-de-Lacerda ◽  
Marcia Barbosa Aguila
Keyword(s):  
Signaling Pathway ◽  
Pancreatic Islet ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Insulin Signaling Pathway ◽  
High Fat ◽  
Adult Mice

scholarly journals Influence ofOreocnide integrifolia(Gaud.) Miq on IRS-1, Akt and Glut-4 in Fat-Fed C57BL/6J Type 2 Diabetes Mouse Model

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Ansarullah ◽  
Selvaraj Jayaraman ◽  
Anandwardhan A. Hardikar ◽  
A. V. Ramachandran
Keyword(s):  
Signaling Pathway ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Therapeutic Potential ◽  
Insulin Signaling Pathway ◽  
High Fat ◽  
Isolated Pancreatic Islets ◽  
Glut 4

Oreocnide integrifolia(OI) leaves are used as folklore medicine by the people of northeast India to alleviate diabetic symptoms. Preliminary studies revealed hypoglycemic and hypolipidemic potentials of the aqueous leaf extract. The present study was carried out to evaluate whether the OI extract induces insulin secretionin vivoandin vitroand also whether it is mediated through the insulin-signaling pathway. The experimental set-up consisted of three groups of C57BL/6J mice strain: (i) control animals fed with standard laboratory diet, (ii) diabetic animals fed with a high-fat diet for 24 weeks and (iii) extract-supplemented animals fed with 3% OI extract along with high-fat diet for 24 weeks. OI-extract supplementation lowered adiposity and plasma glucose and insulin levels. Immunoblot analysis of IRS-1, Akt and Glut-4 protein expressions in muscles of extract-supplemented animals revealed that glucoregulation was mediated through the insulin-signaling pathway. Moreover, immunostaining of pancreas revealed increased insulin immunopositive cells in OI-extract-treated animals. In addition, the insulin secretogogue ability of the OI extract was demonstrated when challenged with high glucose concentration using isolated pancreatic isletsin vitro. Overall, the present study demonstrates the possible mechanism of glucoregulation of OI extract suggestive of its therapeutic potential for the management of diabetes mellitus.

scholarly journals Obesity induced by high-fat diet promotes insulin resistance in the ovary

2010 ◽  
Vol 206 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Eliana H Akamine ◽  
Anderson C Marçal ◽  
João Paulo Camporez ◽  
Mara S Hoshida ◽  
Luciana C Caperuto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Insulin Signaling Pathway ◽  
Female Rats ◽  
High Fat ◽  
Obese Rats

Besides the effects on peripheral energy homeostasis, insulin also has an important role in ovarian function. Obesity has a negative effect on fertility, and may play a role in the development of the polycystic ovary syndrome in susceptible women. Since insulin resistance in the ovary could contribute to the impairment of reproductive function in obese women, we evaluated insulin signaling in the ovary of high-fat diet-induced obese rats. Female Wistar rats were submitted to a high-fat diet for 120 or 180 days, and the insulin signaling pathway in the ovary was evaluated by immunoprecipitation and immunoblotting. At the end of the diet period, we observed insulin resistance, hyperinsulinemia, an increase in progesterone serum levels, an extended estrus cycle, and altered ovarian morphology in obese female rats. Moreover, in female obese rats treated for 120 days with the high-fat diet, the increase in progesterone levels occurred together with enhancement of LH levels. The ovary from high-fat-fed female rats showed a reduction in the insulin receptor substrate/phosphatidylinositol 3-kinase/AKT intracellular pathway, associated with an increase in FOXO3a, IL1B, and TNFα protein expression. These changes in the insulin signaling pathway may have a role in the infertile state associated with obesity.

scholarly journals Salidroside Modulates Insulin Signaling in a Rat Model of Nonalcoholic Steatohepatitis

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Hongshan Li ◽  
Hao Ying ◽  
Airong Hu ◽  
Dezhou Li ◽  
Yaoren Hu
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Insulin Signaling ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Insulin Signaling Pathway ◽  
Hepatic Tissue ◽  
Therapeutic Effects ◽  
High Fat

A growing body of evidence has shown the beneficial effects of salidroside in cardiovascular and metabolic diseases. This study aimed to evaluate the therapeutic effects of salidroside on nonalcoholic steatohepatitis (NASH) in rats and explore the underlying mechanisms related to insulin signaling. A rat model of NASH was developed by high-fat diet for 14 weeks. From week 9 onward, the treatment group received oral salidroside (4.33 mg/kg) daily for 6 weeks. Salidroside effectively attenuated steatosis and vacuolation of hepatic tissue, with a dramatic decrease in liver triglycerides and free fatty acid levels (P < 0.01). Dysregulation of FINS, FBG, HOMA-IR, ALT, and AST in serum was ameliorated with salidroside treatment (P < 0.01). In the liver, salidroside induced significant increases in key molecules in the insulin signaling pathway, such as phosphorylated insulin receptor substrate 1 (IRS1), phosphoinositide 3-kinase (PI3K), and protein kinase B (PKB), with a significant decrease in SREBP-1c levels (P < 0.01). Therefore, salidroside effectively protected rats from high-fat-diet-induced NASH, which may be partially attributed to its effects on the hepatic insulin signaling pathway.

Chlorella modulates insulin signaling pathway and prevents high-fat diet-induced insulin resistance in mice

Life Sciences ◽  
2014 ◽  
Vol 95 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Juliana Falcato Vecina ◽  
Alexandre Gabarra Oliveira ◽  
Tiago Gomes Araujo ◽  
Sueli Regina Baggio ◽  
Cristiane Okuda Torello ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Insulin Signaling Pathway ◽  
High Fat

scholarly journals Resveratrol improves skeletal muscle insulin resistance through downregulating lncRNA NONMMUT044897.2

2021 ◽  
Author(s):  
Zhihong Liu ◽  
Zhimei Zhang ◽  
Guangyao Song ◽  
Xing Wang ◽  
Hanying Xing ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
High Throughput Sequencing ◽  
Insulin Signaling Pathway ◽  
Cytokine Signaling ◽  
Mice Model ◽  
High Fat

Abstract Background: Long non-coding RNA (lncRNA) has proved to be crucial factors in the progression of insulin resistance (IR). Resveratrol (RSV) exhibits promising therapeutic potential for the IR. Nonetheless, whether RSV could influence the expression of lncRNAs and the interaction mechanisms in IR remain unclear.Methods: We conducted high-throughput sequencing to detect the lncRNAs and mRNAs expression signatures and the co-expression network of lncRNAs and mRNAs in skeletal muscle after a high-fat diet (HFD)-induced IR mice model with or without RSV treatment, including hierarchical clustering, gene enrichment and gene co-expression networks analysis. Highly differentially expressed lncRNAs were selected and validated by RT-qPCR. Finally, the biological functions of the selected lncRNAs were investigated by silencing expressing the target genes through lentivirus transfection in C2C12 mouse myotubes cells.Results: We revealed that 338 mRNAs and 629 lncRNAs whose expression in skeletal muscle after a high-fat diet (HFD)-induced IR mice model was reversed by RSV treatment. Gene Ontology and Kyoto encyclopedia of genes and genomes databases indicated that the differential expression mRNAs modulate the insulin signaling pathway. After validating randomly selected lncRNAs via RT-qPCR, we found that lncRNA (NONMMUT044897.2) and Suppressor of Cytokine Signaling 1 (SOCS1) were up-regulated in the HFD group, and reversed by RSV treatment. Additionally, NONMMUT044897.2 was validated to function as a ceRNA of microRNA (miR)-7051-5p and SOCS1 was confirmed as a target for miR‑7051-5p. We further performed lentivirus transfection to knockdown NONMMUT044897.2 in vitro and found that NONMMUT044897.2 silence inactivated SOCS1 and promoted the insulin signaling pathway. Importantly, RSV could mimic the effects of silencing NONMMUT044897.2.Conclusion: Our study revealed that resveratrol improves skeletal muscle IR might be via regulation of NONMUT044897.2.

scholarly journals Effects of Distinct n-6 to n-3 Polyunsaturated Fatty Acid Rations on Insulin Resistant and AD-like Phenotypes in High-Fat Diets-Fed APP/PS1 Transgenic Mice

2021 ◽  
Author(s):  
Xiaojun Ma ◽  
Yujie Guo ◽  
Pengfei Li ◽  
Jingjing Xu ◽  
Shengqi Dong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
High Fat ◽  
Pufa Ratio ◽  
Pro Inflammatory Cytokines

Abstract Background: Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are two prevalent diseases with comparable pathophysiological features and genetic predisposition. Polyunsaturated fatty acids (PUFAs) are essential in maintaining normal brain function. However, little is known about the impact of dietary n-6/n-3 PUFA ratio on AD-like pathology, especially in high-fat diet (HFD)-fed AD model mice. Methods: In the present study, the APP/PS1 mice were treated with 60% HFD for 3.5 months to induced insulin resistance. After that, 45% HFD with different n-6/n-3 PUFA ratios (n-6/n-3=1:1, 5:1 or 16:1) was applied for additional 3.5 months treatment. Following the dietary intervention, the behavior of mice was observed using the Water maze. Following behavioral testing, the animals were euthanized, and serum and tissue samples were collected for biochemical, histological and pathological analyses and evaluation. Cortical fatty acid profile was measured by gas chromatography. Western Blot and immunohistochemistry methods were used to detect protein expression of molecules related to AD pathology and insulin signaling pathway(s) in the brain sample tissues. Immunofluorescence assay was used to uncover the expression and migration of NF-κB in the cortex. qPCR method was applied to determine the gene expression of cortical pro-inflammatory cytokines.Results: HFD caused insulin resistance, increased serum IL-6 and TNF-α level, elevated cortical soluble Aβ1-40, Aβ1-42 content, and increased brain n-6/n-3 PUFAs ratio in APP/PS1 mice. Increased APP and BACE1 protein expression and p-IR/IR ratio, but decreased pro-inflammatory cytokines mRNA expression was observed in the cortex from 60% HFD-fed APP/PS1 mice. N-3 PUFAs rich diet (n-6/n-3=1:1) relieved insulin resistance and hyperlipidemia induced by 60% HFD. Cortical soluble Aβ1-40 and Aβ1-42 contents, the expression of cortical APP, GLUT3, insulin metabolism related molecules, and NF-κB pathway downstream pro-inflammatory cytokines showed a dietary n-6/n-3 PUFAs ratio-dependent way, indicating that dietary n-6/n-3 PUFA ratio plays a critical role in modifying the responses of serum inflammatory cytokine, AD pathology, cortical n-6/n-3 PUFAs ratio, insulin signaling and neuroinflammation to HFD treatment.Conclusion: Dietary n-6/n-3 PUFA ratio play an important role in modifying AD pathophysiology, insulin signaling pathway, and neuro-inflammation response to high fat diet treatment in brain.

scholarly journals Hypochlorous acid via peroxynitrite activates protein kinase Cθ and insulin resistance in adipocytes

2014 ◽  
Vol 54 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Jun Zhou ◽  
Qilong Wang ◽  
Ye Ding ◽  
Ming-Hui Zou
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Hypochlorous Acid ◽  
Insulin Signaling Pathway ◽  
Serine Phosphorylation ◽  
Impaired Insulin ◽  
Genetic Deletion

We recently reported that genetic deletion of myeloperoxidase (MPO) alleviates obesity-related insulin resistance in mice in vivo. How MPO impairs insulin sensitivity in adipocytes is poorly characterized. As hypochlorous acid (HOCl) is a principal oxidant product generated by MPO, we evaluated the effects of HOCl on insulin signaling in adipocytes differentiated from 3T3-L1 cells. Exposure of 3T3-L1 adipocytes to exogenous HOCl (200 μmol/l) attenuated insulin-stimulated 2-deoxyglucose uptake, GLUT4 translocation, and insulin signals, including tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) and phosphorylation of Akt. Furthermore, treatment with HOCl induced phosphorylation of IRS1 at serine 307, inhibitor κB kinase (IKK), c-Jun NH2-terminal kinase (JNK), and phosphorylation of PKCθ (PKCθ). In addition, genetic and pharmacological inhibition of IKK and JNK abolished serine phosphorylation of IRS1 and impairment of insulin signaling by HOCl. Furthermore, knockdown of PKCθ using siRNA transfection suppressed phosphorylation of IKK and JNK and consequently attenuated the HOCl-impaired insulin signaling pathway. Moreover, activation of PKCθ by peroxynitrite was accompanied by increased phosphorylation of IKK, JNK, and IRS1-serine 307. In contrast, ONOO− inhibitors abolished HOCl-induced phosphorylation of PKCθ, IKK, JNK, and IRS1-serine 307, as well as insulin resistance. Finally, high-fat diet (HFD)-induced insulin resistance was associated with enhanced phosphorylation of PKCθ, IKK, JNK, and IRS1 at serine 307 in white adipose tissues from WT mice, all of which were not found in Mpo knockout mice fed HFDs. We conclude that HOCl impairs insulin signaling pathway by increasing ONOO− mediated phosphorylation of PKCθ, resulting in phosphorylation of IKK/JNK and consequent serine phosphorylation of IRS1 in adipocytes.

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